A Phase Ib/II Study of BC3402, a Novel Anti-TIM3 Agent, in Combination With Tremelimumab Plus Durvalumab (STRIDE) in Advanced, Unresectable Hepatocellular Carcinoma

The purpose of this study is to test the safety and efficacy of an investigational (experimental) product called BC3402. This product is considered experimental because it is not approved by the U.S. Food and Drug Administration (FDA).

Start Date01 Jun 2025

Sponsor / Collaborator

The Case Comprehensive Cancer Center

NCT06855225

/ Not yet recruitingPhase 2IIT

A Phase II Study of Single Tremelimumab with Regular Interval Durvalumab (STRIDE) Plus Gemcitabine and Cisplatin (GEMCIS) in Locally Advanced Unresectable/metastatic Combined Hepatocellular-cholangiocarcinoma (cHCC-CCA)

This is a single arm phase 2 study of Single Tremelimumab with Regular Interval Durvalumab (STRIDE) plus Gemcitabine and Cisplatin (GEMCIS) in locally advanced unresectable/metastatic combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Cycles 1 through 8 will be in 3 week intervals and Cycles 9+ will be in 4 week intervals. Tremelimumab is administered at 300mg intravenously once at Cycle 1. Durvalumab is administered at 1500mg intravenously every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+. Gemcitabine is administered at 1000mg/m^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. Cisplatin is administered at 25mg/m^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur at screening and then every 9 weeks until the end of Cycle 9. Disease assessments will then occur every 8 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months treatment from Cycle 1 Day 1 is allowed.

Start Date01 Jun 2025

Sponsor / Collaborator

Hoosier Cancer Research Network

[+2]

NCT06880523

/ Not yet recruitingPhase 2IIT

A Phase II Study of STRIDE (durvalumab + Tremelimumab) with Lenvatinib Versus STRIDE Alone in Patients with Unresectable Hepatocellular Carcinoma (SLIDE-HCC)

The purpose of this study is to compare the effects on participants' and liver cancer by adding a drug that is used on its own to treat this disease to a combination of two other drugs which is also used to treat liver cancer, compared to the two-drug combination alone.

Start Date31 May 2025

Sponsor / Collaborator

Canadian Cancer Trials Group

[+2]

100 Clinical Results associated with Tremelimumab

100 Translational Medicine associated with Tremelimumab

100 Patents (Medical) associated with Tremelimumab

603

Literatures (Medical) associated with Tremelimumab

31 Dec 2025·mAbs

Engineered ipilimumab variants that bind human and mouse CTLA-4

Article

Author: Barman, Ishita ; Lee, Peter S. ; Diong, SJ ; Bee, Christine ; Rajpal, Arvind ; Kumar, Anusha ; West, Sean M. ; Chau, Bryant ; Strop, Pavel ; Robison, Brett ; Chang, Olin ; Korman, Alan J. ; Moon, Thomas M.

Testing of candidate monoclonal antibody therapeutics in preclinical models is an essential step in drug development. Identification of antibody therapeutic candidates that bind their human targets and cross-react to mouse orthologs is often challenging, especially for targets with low sequence homology. In such cases, surrogate antibodies that bind mouse orthologs must be used. The antibody 9D9, which binds mouse CTLA-4, is a commonly used surrogate for CTLA-4 checkpoint blockade studies in mouse cancer models. In this work, we reveal that 9D9 has significant biophysical dissimilarities to therapeutic CTLA-4 antibodies. The 9D9-mCTLA4 complex crystal structure was determined and shows that the surrogate antibody binds an epitope distinct from ipilimumab and tremelimumab. In addition, while ipilimumab has pH-independent binding to hCTLA-4, 9D9 loses binding to mCTLA-4 at physiologically relevant acidic pH ranges. We used phage and yeast display to engineer ipilimumab to bind mouse CTLA-4 with single-digit nM affinity from an initial state with no apparent binding. The engineered variants showed pH-independent and cross-reactive binding to both mouse and human CTLA-4. Crystal structures of a variant in complex with both mouse and human CTLA-4 confirmed that it targets an equivalent epitope as ipilimumab. These cross-reactive ipilimumab variants may facilitate improved translatability and future mechanism-of-action studies for anti-CTLA-4 targeting in murine models.

01 Dec 2025·Journal of Gastrointestinal Cancer

The Efficacy and Safety of Durvalumab and Tremelimumab with Concomitant Treatment for MSS/pMMR Metastatic Colorectal Cancer: A Single Arm Meta-Analysis

Article

Author: Zhang, Danning ; Chen, Tianyu

OBJECTIVES:

To address the issue that most microsatellite-stable (MSS) and proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) patients have minimal response to immunotherapy, this meta-analysis evaluated the efficacy and safety of durvalumab and tremelimumab with concomitant treatment in treating MSS/pMMR metastatic colorectal cancer.

METHODS:

All included trials were prospective studies with a median patient age of 63 years, of which 94.2% were MSS/pMMR mCRC patients, with a male to female ratio of 1.5:1. Based on durvalumab and tremelimumab treatment, one study performed surgical resection on resectable cases, while the other four studies performed radiotherapy or chemotherapy on unresectable cases. Analyses include objective response rate (ORR).etc. for drug activity, overall survival (OS) and progression-free survival (PFS) for therapeutic efficacy, and adverse events (AEs) for safety. The risk of bias was assessed by sensitivity analysis.

RESULTS:

5 studies involving 228 patients were included in this meta-analysis. The pooled estimates showed a median OS of 9.26 months, median PFS of 2.53 months, partial response (PR) of 13.6%, stable disease (SD) of 32.8%, ORR of 12.5% and disease control rate (DCR) of 65.4%. AEs were generally low, with pruritus (27.5%), diarrhea (28.8%), and fatigue (53.9%) being the most common, while other AEs occurred at less frequencies.

CONCLUSIONS:

Durvalumab and tremelimumab with concomitant treatment for MSS/pMMR mCRC patients is relatively effective and safe, which is helpful in addressing the problem of mCRC with MSS/pMMR that has minimal response to immunotherapy.

01 Apr 2025·Hepatology (Baltimore, Md.)

The rapidly evolving landscape of HCC: Selecting the optimal systemic therapy

Review

Author: Rimassa, Lorenza ; Braconi, Chiara ; Zanuso, Valentina

Over the past years, there has been a remarkable advance in the systemic treatment options for advanced HCC. The overall survival has gradually increased over time, with larger benefits for patients with sensitive tumors and preserved liver function, the latter being an essential condition for the delivery of sequential lines of treatment and optimization of clinical outcomes. With the approval of new first-line agents and the introduction of immune checkpoint inhibitor-based therapies, the treatment landscape of advanced HCC is becoming wider than ever. Atezolizumab plus bevacizumab and, more recently, durvalumab plus tremelimumab have entered the clinical practice and are the current standard of care for treatment-naïve patients, surpassing sorafenib and lenvatinib monopoly. As no head-to-head comparisons are available among all the first-line treatment options, the recommendation for the most appropriate choice and sequence is patient-driven and integrates efficacy data with clinical comorbidities, background liver disease, and the safety profile of available drugs. In addition, predictive biomarkers for successful patients’ stratification are yet to be available and constitute the focus of ongoing research. The treatment algorithm is likely to become even more complex since systemic therapeutic approaches are now being translated into earlier stages of the disease, with an impact on the evolution of the sequential treatment of patients with HCC.

257

News (Medical) associated with Tremelimumab

25 Mar 2025

·www.astrazeneca.com

New study results reinforce Tagrisso as the backbone therapy for EGFR-mutated lung cancer across stages and settings

New study results presented at the European Lung Cancer Congress (ELCC) 2025, 26 to 29 March, demonstrate the role of AstraZeneca’s Tagrisso (osimertinib), as monotherapy and as the backbone for novel combinations, across stages and settings of epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Highlights include: LAURA Phase III trial of Tagrisso in unresectable, Stage III EGFRm NSCLC after chemoradiotherapy (CRT) (LBA4). SAVANNAH Phase II trial of Tagrisso plus Orpathys (savolitinib) in advanced EGFRm NSCLC with high levels of MET overexpression and/or amplification following disease progression on 1st-line Tagrisso (#2O). ORCHARD Phase II platform trial of Tagrisso plus Datroway (datopotamab deruxtecan) in advanced EGFRm NSCLC following disease progression on 1st-line Tagrisso (#1O). FLAURA2 Phase III trial of Tagrisso plus chemotherapy as 1st-line treatment for advanced EGFRm NSCLC (#53P). Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, said: “A critical goal in treating every patient with lung cancer is to not only extend a patient's life but also maintain quality of life while on treatment. The continued overall survival trend seen here at ELCC in the unresectable Stage III setting and the promising data for combinations that can address progression in the advanced setting, together reinforce osimertinib as an effective, safe and convenient treatment for patients with EGFR-mutated lung cancer across stages and lines of treatment.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Having now treated more than one million patients around the world, Tagrisso has repeatedly transformed expectations for patients with EGFR-mutated lung cancer by not only extending survival but also showing it is possible to maintain quality of life during cancer treatment. The breadth of data at ELCC reinforce Tagrisso as the backbone therapy for patients with this disease and show that adding Orpathys or Datroway at the time of disease progression can help prolong patients’ responses to treatment.” Professor Virginia Harrison, EGFR Positive UK, said: “For people undergoing treatment for lung cancer, maintaining quality of life is so important, but it can be challenging. The development of simple and effective treatment regimens that minimise negative side effects can make a huge difference. We are excited to see this progress for patients with EGFR-mutated lung cancer, where there is still significant unmet need.” Tagrisso continued to demonstrate encouraging overall survival (OS) trend in unresectable, Stage III setting in LAURA trial Updated results from the LAURA Phase III trial showed an improved trend towards OS benefit with Tagrisso compared to placebo in patients with unresectable, Stage III EGFRm NSCLC (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.40, 1.14, maturity 31%). Median OS was 58.8 months (95% CI 54.1, not calculable [NC]) in patients treated with Tagrisso versus 54.1 months with placebo (95% CI 42.1, NC), despite 78% of patients on placebo receiving subsequent treatment with Tagrisso upon progression. The trial will continue to assess OS as a key secondary endpoint at the final analysis. Tagrisso previously demonstrated a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS). These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU and China. Safety results and discontinuation rates due to adverse events (AEs) were as expected and no new safety concerns were identified. Tagrisso plus Orpathys showed durable response rates in lung cancer patients with high levels of MET overexpression and/or amplification whose disease progressed on 1st-line Tagrisso in SAVANNAH trial Results from the SAVANNAH Phase II trial showed Tagrisso plus Orpathys (300mg twice-daily [BID]) demonstrated a clinically meaningful and durable objective response rate (ORR) in patients with EGFRmNSCLC with high levels of MET overexpression and/or amplification whose disease progressed on treatment with 1st-line Tagrisso. Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cut-off. Tagrisso plus Orpathys demonstrated a confirmed ORR of 56% (95% CI 45-67%), with a median duration of response (DoR) of 7.1 months (95% CI 5.6-9.6). Median PFS (mPFS) was 7.4 months (95% CI 5.5-7.6). Safety results and discontinuation rates due to AEs were consistent with the established profiles of each medicine and no new safety concerns were reported. In all patients treated with Tagrisso plus Orpathys (300mg BID), Grade 3 or higher AEs occurred in 57% of patients. Orpathys is an oral, potent and highly selective MET tyrosine kinase inhibitor (TKI) being jointly developed and commercialised by AstraZeneca and HUTCHMED. In 2023, Tagrisso plus Orpathys received Fast Track designation from the Food and Drug Administration (FDA) in this setting. Tagrisso plus Datroway showed encouraging response rates in patients whose disease progressed on 1st-line Tagrisso in ORCHARD trial First results from the Tagrisso plus Datroway module of the ORCHARD Phase II platform trial showed the combination demonstrated promising efficacy and manageable safety in patients with advanced EGFRm NSCLC whose disease progressed on treatment with Tagrisso. The module enrolled an all-comer population of patients with EGFRmNSCLC and evaluated two doses of Datroway (4 or 6mg/kg) which, in combination with Tagrisso, showed similar ORRs of 43% (80% CI 31-55%) and 36% (80% CI 25-49%), respectively. PFS and DoR results favoured the 6mg/kg dose with a mPFS of 11.7 months (95% CI 8.3, NC) and 64% of patients continuing to respond at 9 months versus a mPFS of 9.5 months (95% CI 7.2-9.8) and 15% of patients continuing to respond at 9 months on the 4mg/kg dose. The safety profile of Tagrisso plus Datroway was consistent with the known safety profiles of each medicine and no new safety concerns were identified at either dose level. Grade 3 or higher treatment-related AEs occurred in 34% and 56% of patients receiving the 4mg/kg or 6mg/kg doses, respectively. Datroway is a specifically engineered TROP2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. The Companies are evaluating Datroway alone and with Tagrisso as treatment for patients with advanced or metastatic EGFRm NSCLC in the TROPION-Lung14 and TROPION-Lung15 Phase III trials. New results for Tagrisso plus chemotherapy in the 1st-line setting reinforce strong PFS benefit in FLAURA2 Phase III trial An exploratory post-hoc analysis of the FLAURA2 Phase III trial assessed PFS by length of exposure to pemetrexed maintenance treatment in patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso with the addition of chemotherapy (pemetrexed plus cisplatin) followed by maintenance treatment with Tagrisso and chemotherapy (pemetrexed) or Tagrisso alone. Results showed an mPFS of more than two years regardless of length of pemetrexed maintenance exposure, with a trend associating longer PFS with longer pemetrexed treatment. The safety profile of Tagrisso plus chemotherapy was consistent with the established profiles of the individual medicines. Grade 3 or higher chemotherapy-related AEs were reported in 16% of patients who received maintenance treatment for 3 to less than 9 months, and 10% for patients who received maintenance for 9 or more months. Chemotherapy discontinuation rates due to AEs were 18% and 10%, respectively. Tagrisso plus chemotherapy previously demonstrated a statistically significant and clinically meaningful improvement in PFS. These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU, Japan and China. Previously presented OS data from the second interim analysis showed a favourable trend with the Tagrisso plus chemotherapy arm (HR 0.75; 95% CI 0.57-0.97, maturity 41%), with consistent results across all prespecified subgroups. The trial will continue to assess OS as a key secondary endpoint. Notes NSCLC Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for about 80% of cases.2 Approximately 10 to 15% of patients with NSCLC in the US and Europe and 30 to 40% of patients in Asia have an EGFR mutation.3-5 While EGFR-TKIs have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.6-9 LAURA LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with Tagrisso 80mg once-daily (QD) oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with Tagrisso. The trial enrolled 216 patients in more than 145 centres across more than 15 countries, including in the US, Europe, South America and Asia. SAVANNAH SAVANNAH is an ongoing randomised, global Phase II trial studying the efficacy of Orpathys added to Tagrisso in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification whose disease progressed following treatment with Tagrisso. Based on the original single-arm trial design, patients were treated with Orpathys 300 or 600mg QD or 300mg BID, in combination with oral Tagrisso 80mg QD. In 2022, a comparison of Orpathys 300mg BID and Tagrisso 80mg QD to Orpathys 300mg BID and placebo was added to the trial to evaluate contribution of components. The trial has enrolled 369 patients to date in more than 80 centres globally, including in the US, Canada, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include PFS and DoR. In August 2022, positive interim ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC). The global SAFFRON Phase III trial will further assess the Tagrisso plus Orpathys combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following treatment with Tagrisso. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH. ORCHARD ORCHARD (Osimertinib Resistance CoHorts, Addressing 1L Relapse Drivers) is an open-label, multi-centre Phase II platform trial evaluating numerous Tagrisso-based combinations as a treatment for patients with advanced EGFRm NSCLC whose disease has progressed on 1st-line Tagrisso. The trial has 10 modules examining the efficacy, safety and tolerability of these targeted and non-targeted combination options, including Tagrisso 80mg QD plus Datroway given intravenously at 4 or 6mg/kg on day one of every three-week cycle. The trial has enrolled 247 patients to date in more than 40 centres globally, including in the US, Europe and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS and DoR. FLAURA2 FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg QD oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS. Tagrisso Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Tagrisso (40mg and 80mg QD oral tablets) has been used to treat patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC. There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. Orpathys Orpathys (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumours. MET is a tyrosine kinase receptor that has an essential role in normal cell development. Orpathys blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression. MET overexpression and/or amplification can lead to tumour growth and the metastatic progression of cancer cells, and is a known mechanism of acquired resistance to EGFR TKIs. The prevalence of MET depends on the sample type, detection method and assay cut-off used. Orpathys is approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations. It is currently under clinical development for multiple tumour types, including lung, kidney and gastric cancers as a single treatment and in combination with other medicines. Datroway Datroway (datopotamab deruxtecan-dlnk in the US; datopotamab deruxtecan in rest of world) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Datroway (6mg/kg) is approved in the US, Japan and Russia for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 Phase III trial. In the US, a Biologics License Application for Datroway is under Priority Review for the treatment of adult patients with locally advanced or metastatic EGFRm NSCLC who have received prior systemic therapies, including an EGFR-directed therapy. Datroway was also granted Breakthrough Therapy Designation by the FDA for this patient population. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and Datroway in collaboration with Daiichi Sankyo; Orpathys in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Oncology Corporate and financial

Clinical ResultPhase 3Phase 2Drug ApprovalFast Track

21 Mar 2025

·www.fiercepharma.com

FDA rejects Hengrui, Elevar's PD-1 cancer drug combination—again

The FDA has raised new issues at Jiangsu Hengrui Pharmaceuticals' camrelizumab manufacturing plant after a reinspection of the facility in January 2025. Jiangsu Hengrui Pharmaceuticals and its partner Elevar Therapeutics will have to wait even longer before their PD-1 inhibitor camrelizumab can enter the U.S. market.The FDA has once again issued a complete response letter to Hengrui and Elevar’s applications for camrelizumab and the VEGFR inhibitor rivoceranib as a combination for the first-line treatment of liver cancer, Hengrui said in securities filing (PDF, Chinese) to Shanghai Stock Exchange.The FDA first snubbed the combo in May 2024 due to deficiencies it identified during an inspection of a Hengrui manufacturing facility in China. The agency also cited an incomplete clinical trial site inspection as another reason for the prior rejection.This time around, in the new CRL, the FDA again raised manufacturing issues that require responses from Hengrui, although the agency didn’t spell out specific reasons, Hengrui said in the filing.“The company will keep close communication with the FDA and will take measure as soon as possible upon confirming the specific reasons and resubmit the application, in hopes of obtaining an approval,” Hengrui said.During the first review cycle for the combo, U.S. regulators issued a 10-page, 10-observation Form 483 to Hengrui’s subsidiary, Suzhou Suncadia Biopharmaceuticals. At the firm’s Suzhou facility, which produces camrelizumab, FDA inspectors in 2023 found myriad problems regarding protection of data integrity, prevention against microbiological contamination, potential mix-ups between raw materials meant for the Chinese and U.S. markets, and other issues. Following that first CRL, Hengrui and Elevar quickly refiled their applications, which the FDA accepted in October 2024. The pair also updated their data package to include the final analysis from the phase 3 Cares-310 trial, which showed that the camrelizumab-rivoceranib combo reduced patients' risk of death by 36% versus Bayer’s Nexavar in those with first-line unresectable hepatocellular carcinoma. Patients who received the combo lived a median 23.8 months, compared with 15.2 months for the control group.The FDA conducted a reinspection of the Hengrui plant in January 2025 and confirmed that all shortfalls spotted in the previous CRL were resolved, Hengrui said, according to multiple Chinese media reports. But this time, the U.S. agency raised three new issues for improvement, and Hengrui has already responded to the agency's concerns stemming from that inspection, the company said.Because rivoceranib, which carries a brand name Tulvegio, is used as part of a combination with camrelizumab, the FDA cannot approve the VEGFR inhibitor alone, Elevar’s parent company, HLB, said in a filing to the Korea Exchange.“We were not anticipating the FDA’s decision based on recent final label negotiations and positive interactions with the FDA,” Elevar CEO Saeho Chong, Ph.D., said in a statement to Fierce Pharma. Chong stressed that the FDA didn’t raise any issues about clinical data or rivoceranib and that the rejection was “solely to unresolved site remediation at the camrelizumab facility.” Roche’s combination of the PD-L1 inhibitor Tecentriq, used together with bevacizumab, is a standard combination for first-line liver cancer in the U.S. AstraZeneca’s immunotherapy duo of Imfinzi and Imjudo is also an option. Bristol Myers Squibb is awaiting an FDA decision for its PD-1/CTLA-4 cocktail of Opdivo and Yervoy in the same condition, with a target decision date set for April 21.Outside the U.S., Elevar plans to submit an application for camrelizumab and rivoceranib in first-line liver cancer to the European Medicines Agency in September 2025, according to the company. The combo was first cleared in that indication in China in January 2023.Editor's Note: The story was updated with additional comments from Elevar.

Clinical ResultDrug ApprovalPhase 3ImmunotherapyNDA

17 Mar 2025

·pipelinereview.com

Imfinzi approved in the EU as first and only immunotherapy for limited-stage small cell lung cancer

Approval based on ADRIATIC Phase III trial results which showed a 27% reduction in the risk of death versus placebo LONDON, UK I March 17, 2025 I AstraZeneca’s Imfinzi (durvalumab) has been approved in the European Union (EU) as monotherapy for the treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy (CRT). The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the ADRIATIC Phase III trial, which were published in The New England Journal of Medicine . SCLC is a highly aggressive form of lung cancer, with an estimated 8,000 people treated for LS-SCLC across the five major European countries each year. 1-2 LS-SCLC typically recurs and progresses rapidly, despite initial response to standard-of-care chemotherapy and radiotherapy. 3-4 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients survive for five years after diagnosis. 5 Suresh Senan, PhD, radiation oncologist at the Amsterdam University Medical Centers, The Netherlands, and principal investigator in the trial, said: “This approval marks a turning point for patients with limited-stage small cell lung cancer in Europe, bringing them an immunotherapy option for the first time. An unprecedented 57% of patients treated with durvalumab were still alive at three years in the ADRIATIC trial. This significant advance establishes a new benchmark in a setting where the standard of care has remained unchanged for decades.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Imfinzi has the potential to transform how limited-stage small cell lung cancer is treated as the first immunotherapy approved in Europe in this setting. As the only immunotherapy approved for both early and late-stage disease, Imfinzi is poised to become the foundation for transforming outcomes for people with small cell lung cancer.” In the trial, results showed Imfinzi reduced the risk of death by 27% versus placebo (based on an overall survival [OS] hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% for placebo. Imfinzi also reduced the risk of disease progression or death by 24% (based on a progression-free survival [PFS] HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% for placebo. The safety profile for Imfinzi was generally manageable and consistent with the known profile of this medicine. No new safety signals were observed. Imfinzi is approved in the US and several other countries in this setting based on the ADRIATIC results. Regulatory applications are currently under review in Japan and several other countries for this indication. Imfinzi is also approved in combination with chemotherapy for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. Notes Small cell lung cancer Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. 6-7 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% of cases classified as SCLC. 8 LS-SCLC (Stage I-III) accounts for approximately 30% of SCLC diagnoses and is classified when the disease is generally only in one lung or one side of the chest. 9 The prognosis for patients with LS-SCLC remains poor despite curative-intent treatment with standard-of-care concurrent CRT (cCRT). 10 ADRIATIC The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months. The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe and Asia. Imfinzi Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune response s. In addition to its indications in SCLC, Imfinzi is also the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after CRT. Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC; and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU. In March 2025, perioperative Imfinzi added to standard-of-care chemotherapy met the primary endpoint of event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers. Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1 st -line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi . As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi and Imjudo ; Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References 1. National Cancer Institute. NCI Dictionary – Small Cell Lung Cancer. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer . Accessed March 2025. 2. AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html . Accessed March 2025. 3. Qin A, Kalemkerian GP. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? J Oncol Pract . 2018;14(6):369-370. 4. Cheng Y, et al. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med . 2024;391(14):1313-1327. 5. Bebb DG, et al. Symptoms and Experiences with Small Cell Lung Cancer: A Mixed Methods Study of Patients and Caregivers. Pulm Ther . 2023;9:435-450. 6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed March 2025. 7. World Health Organization. International Agency for Research on Cancer. World Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/populations/900-world-fact-sheet.pdf . Accessed March 2025. 8. LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer . Accessed March 2025. 9. American Cancer Society. Small Cell Lung Cancer Stages. Available at: https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/staging-sclc.html . Accessed March 2025. 10. Senan S, et al. ADRIATIC: A phase III trial of durvalumab ± tremelimumab after concurrent chemoradiation for patients with limited stage small cell lung cancer. Ann Oncol . 2019;30(suppl. 2):ii25. SOURCE: AstraZeneca

ImmunotherapyPhase 3Clinical ResultDrug Approval

100 Deals associated with Tremelimumab

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KEGG	Wiki	ATC	Drug Bank
D06657	Tremelimumab	-	DB11771

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatocellular Carcinoma	Canada	AstraZeneca Canada, Inc.	31 Aug 2023
Advanced Hepatocellular Carcinoma	European Union	AstraZeneca AB	20 Feb 2023
Advanced Hepatocellular Carcinoma	Iceland	AstraZeneca AB	20 Feb 2023
Advanced Hepatocellular Carcinoma	Liechtenstein	AstraZeneca AB	20 Feb 2023
Advanced Hepatocellular Carcinoma	Norway	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	European Union	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	Iceland	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	Liechtenstein	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	Norway	AstraZeneca AB	20 Feb 2023
Advanced Lung Non-Small Cell Carcinoma	Japan	AstraZeneca KK	23 Dec 2022
Non-Small Cell Lung Cancer	United States	AstraZeneca AB	10 Nov 2022
Unresectable Hepatocellular Carcinoma	United States	AstraZeneca AB	21 Oct 2022

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Muscle Invasive Bladder Neoplasms	Phase 3	United States	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Japan	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Argentina	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Austria	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Brazil	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Canada	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Chile	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	France	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Germany	AstraZeneca PLC	05 Aug 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 3	Greece	AstraZeneca PLC	05 Aug 2021

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03164616 (POSEIDON, ESMO_ELCC2025)	Phase 3	metastatic non-small cell lung cancer First line EGFR/ALK wild-type	175	Durvalumab + Tremelimumab + Chemotherapy	raufqsvjsj(axulisvktu) = D+T+CT demonstrated statistically significant improvements in both progression-free survival (PFS; HR 0.72; 95% CI 0.60-0.86; p = 0.0003) and overall survival (OS; HR 0.77; 95% CI 0.65-0.92; p = 0.0030) vs CT alone, leading to approvals for this regimen. D+CT significantly improved PFS vs CT (0.74; 95% CI 0.62-0.89; p = 0.0009), with a positive trend for OS improvement (HR 0.86; 95% CI 0.72-1.02; p = 0.0758) ltnoxymdia (clvzlqqxnb ) View more	Positive	26 Mar 2025
NCT03164616 (POSEIDON, ESMO_ELCC2025)	Phase 3		175	Durvalumab + Chemotherapy		Positive	26 Mar 2025
NCT02879162 (CTgov)	Phase 2	Advanced cancer	140	Tremelimumab+Durvalumab	yboespitee(nnysphbxve) = vahhycbgtg ygxyvlpwvq (itktqotvqo, mbkfirefzm - pdxfpkwfxx) View more	-	25 Mar 2025
NCT03638141 (ASCO_GI2025) Manual	Phase 2	Hepatocellular Carcinoma	20	Durvalumab + tremelimumab + TACE	flgjvxggwk(mikdjkwgsf) = enzkzagtqp mudhiskrqd (iubxnnugfd, 32 - 77) Met View more	Positive	23 Jan 2025
STRIDE (ASCO_GI2025)	Not Applicable	Unresectable Hepatocellular Carcinoma	79	STRIDE regimen (Tremelimumab 300 mg + Durvalumab 1500 mg)	qbmdtxbfxv(puxawytsyw) = oujzeffynz klfiqggwks (dmcjhcrwln ) View more	-	23 Jan 2025
NCT03702179 (IMMUNOPRESERVE-SOGUG \| IMMUNOPRESERVE, CTgov)	Phase 2	Carcinoma of urinary bladder, invasive \| Muscle Invasive Bladder Carcinoma	32	Radiotherapy+Tremelimumab+Durvalumab	wjghovmxpw = umufsfbvqs uievckcrlv (hjxuwavfmo, gsbgyetkto - eywhebppqy) View more	-	05 Dec 2024
NCT04989218 (ICC, CTgov)	Phase 1/2	Intrahepatic Cholangiocarcinoma	1	Tremelimumab+Gemcitabine+Cisplatin+Durvalumab	zqekpyznuo = uzamtirere swcjyyvsrc (gwgcgrgibm, avnvizpcmy - tuhfdzxnug) View more	-	05 Nov 2024
NCT03116529 (NEXIS, Pubmed \| Cureus) Manual	Phase 1/2	Soft Tissue Sarcoma Neoadjuvant	23	Durvalumab + Tremelimumab	dnegzfygze(sqjqavlryy) = xkcswxpwlg vyenvippnu (zjasckbnib ) View more	Positive	22 Oct 2024
NCT02754856 (CTgov)	Phase 1	Liver metastases \| Colorectal Liver Metastases	24	Durvalumab	ejtvwrmfuw = namozpirvx xrsxxyjfmm (yrxgxzzovt, jppvsrdkxh - dsrlkilyqn) View more	-	09 Oct 2024
NCT03298451 (HIMALAYA, ESMO2024) Manual	Phase 3	Unresectable Hepatocellular Carcinoma	-	STRIDETremelimumabDurvalumab	tcacksrgee(wvndinmxkj) = prtlskexyf rhduzqjoip (nbucaivrqp ) View more	Positive	16 Sep 2024
NCT03298451 (HIMALAYA, ESMO2024) Manual	Phase 3	Unresectable Hepatocellular Carcinoma	-	Durvalumab	tcacksrgee(wvndinmxkj) = oytcqbwxjn rhduzqjoip (nbucaivrqp ) View more	Positive	16 Sep 2024
NCT03899610 (KGOG3046 \| TRU-D, ESMO2024) Manual	Phase 2	Ovarian Cancer Neoadjuvant	45	Neoadjuvant chemotherapy durvalumabltremelimumabtiple low dose of tremelimumab	zmsufrgwtp(apxlaavpga) = lyfvdsietj nvfpuzqgpp (jkbagfulwn ) View more	Positive	14 Sep 2024
NCT03899610 (KGOG3046 \| TRU-D, ESMO2024) Manual	Phase 2	Ovarian Cancer Neoadjuvant	45	Neoadjuvant chemotherapy durvalumabltremelimumabgle high dose of tremelimumab	zmsufrgwtp(apxlaavpga) = iepqovjndy nvfpuzqgpp (jkbagfulwn ) View more	Positive	14 Sep 2024

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