Phase 1 Trial of Safety and Preliminary Efficacy of Segmental Ablative Radioembolization in Combination With Tremelimumab Plus Durvalumab (MEDI4736) in Patients With Unresectable, or Oligo-Metastatic Cholangiocarcinoma Who Are Not Candidates for Curative Therapy (RAIDEN Trial)

This phase I trial tests the safety and side effects of yttrium-90 (Y90) radioembolization combined with immunotherapy drugs tremelimumab and durvalumab in treating patients with intrahepatic cholangiocarcinoma (cancer of the bile ducts in the liver) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) who are not candidates for curative therapy or that has spread from where it first started (primary side) to multiple other places in the body (oligo-metastatic). Cholangiocarcinoma is a rare but aggressive cancer with limited curative options outside of surgery. Immunotherapy has shown modest benefit in hepatobiliary (liver, bile ducts, and gallbladder) cancers including cholangiocarcinoma. Radioembolization is a type of radiation therapy used to treat liver cancer that is advanced or has come back where tiny beads that hold the radioactive substance (radioisotope) yttrium Y90 are injected into or near the hepatic artery (the main blood vessel that carries blood to the liver). The beads collect in the tumor and the Y90 gives off radiation. This destroys the blood vessels that the tumor needs to grow and kills the tumor cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving Y90 radioembolization in combination with tremelimumab and durvalumab immunotherapy may be safe and beneficial in treating patients with locally advanced, unresectable or oligo-metastatic intrahepatic cholangiocarcinoma who are not candidates for curative therapy.

Start Date06 Jun 2024

Sponsor / Collaborator

Mayo Clinic

NCT06017297 / RecruitingPhase 2IIT

Phase II Study of Neoadjuvant Durvalumab (MEDI4736) and Tremelimumab in Combination With Gemcitabine and Cisplatin in Patients With Intrahepatic Cholangiocarcinoma That is Borderline Resectable/Resectable But With High Risk for Recurrence.

The goal of this clinical trial is to test feasibility and safety of the combination of tremelimumab and durvalumab plus gemcitabine and cisplatin as a neoadjuvant treatment bridge patients to a curative resection in treatment naïve borderline resectable, or resectable with high risk for recurrence intrahepatic cholangiocarcinoma patients. The main question[s] it aims to answer are:
What is the rate of conversion of unresectable tumor to resectable cancer?
What are the side effects of this treatment combination?
Participants will undergo an initial tumor biopsy, imaging and laboratory studies prior to starting treatment with durvalumab, tremelimumab, gemcitabine and cisplatin. Participants will continue for 4 cycles and if the tumor is found to be resectable then they will undergo surgical resection. If the tumor is unresectable (can't be surgically removed) after 4 cycles, then participants will receive 4 more cycles and repeated imaging. If the tumor remains unresectable then the participant will be treated with capecitabine for up to 8 cycles and durvalumab for up to 12 months.

Start Date01 Jun 2024

Sponsor / Collaborator

Georgetown University

[+1]

NCT06008093 / RecruitingPhase 3

A Phase IIIb, Randomized, Multicenter, Open-label Study to Assess the Efficacy of Durvalumab Plus Tremelimumab Versus Pembrolizumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Metastatic Non-Small Cell Lung Cancer Patients With Non-Squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS (TRITON).

The purpose of the study is to assess the efficacy of durvalumab plus tremelimumab in combination with chemotherapy compared with pembrolizumab in combination with chemotherapy in metastatic NSCLC patients with non-squamous histology who have mutations and/or co-mutations in STK11, KEAP1, or KRAS.

Start Date04 Apr 2024

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Tremelimumab

100 Translational Medicine associated with Tremelimumab

100 Patents (Medical) associated with Tremelimumab

465

Literatures (Medical) associated with Tremelimumab

01 Mar 2024·Gynecologic oncology

Durvalumab with or without tremelimumab plus chemotherapy in HRR non-mutated, platinum-resistant ovarian cancer (KGOG 3045): A phase II umbrella trial

Article

Author: Lee, Sungyoung ; Choi, Chel Hun ; Park, Eunhyang ; Kim, Yoo-Na ; Chung, Jongsuk ; Park, Junsik ; Kim, Jae-Weon ; Lee, Jung-Yun ; Kim, Hee Seung ; Lee, Jung Bok ; Kim, Sunghoon ; Kim, Se Ik ; Kim, Byoung-Gie ; Lim, Jinyeong ; Joung, Je-Gun

AIM:

We investigated the efficacy and safety of durvalumab (D) with or without tremelimumab (T) in addition to single-agent chemotherapy (CT) in patients with platinum-resistant recurrent ovarian cancer (PROC) lacking homologous recombination repair (HRR) gene mutations.

PATIENTS AND METHODS:

KGOG 3045 was an open-label, investigator-initiated phase II umbrella trial. Patients with PROC without HRR gene mutations who had received ≥2 prior lines of therapy were enrolled. Patients with high PD-L1 expression (TPS ≥25%) were assigned to arm A (D + CT), whereas those with low PD-L1 expression were assigned to arm B (D + T75 + CT). After completing arm B recruitment, patients were sequentially assigned to arms C (D + T300 + CT) and D (D + CT).

RESULTS:

Overall, 58 patients were enrolled (5, 18, 17, and 18 patients in arms A, B, C, and D, respectively). The objective response rates were 20.0, 33.3, 29.4, and 22.2%, respectively. Grade 3-4 treatment-related adverse events were observed in 20.0, 66.7, 47.1, and 66.7 of patients, respectively, but were effectively managed. Multivariable analysis demonstrated that adding T to D + CT improved progression-free survival (adjusted HR, 0.435; 95% CI, 0.229-0.824; P = 0.011). Favorable response to chemoimmunotherapy was associated with MUC16 mutation (P = 0.0214), high EPCAM expression (P = 0.020), high matrix remodeling gene signature score (P = 0.017), and low FOXP3 expression (P = 0.047). Patients showing favorable responses to D + T + CT exhibited significantly higher EPCAM expression levels (P = 0.008) and matrix remodeling gene signature scores (P = 0.031) than those receiving D + CT.

CONCLUSIONS:

Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation.

01 Mar 2024·Neoplasia (New York, N.Y.)

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma – knowledge obtained from the CheckRad-CD8 trial

Article

Author: Donaubauer, Anna-Jasmina ; Brunner, Thomas B ; Laban, Simon ; Fleischmann, Maximilian ; Zhou, Jian-Guo ; Klautke, Gunther ; Fietkau, Rainer ; Iro, Heinrich ; Tianyu, Xie ; Gaipl, Udo S ; Hautmann, Matthias G ; Frey, Benjamin ; Tamaskovics, Bálint ; Gostian, Antoniu-Oreste ; Kist, Andreas M ; Illmer, Thomas ; Döllinger, Michael ; Eckstein, Markus ; Hecht, Markus ; Hartmann, Arndt ; Becker, Ina

PURPOSE:

Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC.

METHODS:

The peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy.

RESULTS:

The tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent.

CONCLUSIONS:

Our analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.

16 Feb 2024·Clinical cancer research : an official journal of the American Association for Cancer Research

Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden

Article

Author: Losonczy, György ; Özgüroğlu, Mustafa ; Paz-Ares, Luis ; Shrestha, Yashaswi ; Xie, Mingchao ; Trukhin, Dmytro ; Jiang, Haiyi ; Chen, Yuanbin ; Mann, Helen ; Ji, Jun Ho ; Hotta, Katsuyuki ; Garassino, Marina Chiara ; Reinmuth, Niels ; Statsenko, Galina ; Godin-Heymann, Nadia ; Havel, Libor ; Bondarenko, Igor ; Poltoratskiy, Artem ; Goldman, Jonathan W ; Conev, Nikolay ; Lai, Zhongwu ; Hochmair, Maximilian J

Abstract:

Purpose::

In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small cell lung cancer (ES-SCLC). We report exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB).

Experimental Design::

Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model.

Results::

The PD-L1 and tTMB biomarker-evaluable populations (BEP) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TC), ≥1% immune cells (IC), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with HRs all falling within the 95% confidence interval (CI) for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP vs. EP, P = 0.916; durvalumab plus tremelimumab plus EP vs. EP, P = 0.672).

Conclusions::

OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset.See related commentary by Rolfo and Russo, p. 652

142

News (Medical) associated with Tremelimumab

25 Jun 2024

·pipelinereview.com

Update on ADJUVANT BR.31 Phase III trial of Imfinzi in non-small cell lung cancer

LONDON, UK I June 25, 2024 I High-level results from the ADJUVANT BR.31 Phase III trial, sponsored by the Canadian Cancer Trials Group (CCTG), showed Imfinzi (durvalumab) did not achieve statistical significance for the primary endpoint of disease-free survival (DFS) versus placebo in early-stage (IB-IIIA) non-small cell lung cancer (NSCLC) after complete tumour resection in patients whose tumours express PD-L1 on 25% or more tumour cells. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “We are disappointed in the ADJUVANT BR.31 results. Imfinzi has helped change the treatment landscape and achieved multiple positive Phase III trials for patients with earlier stages of lung cancer. We are committed to addressing the remaining unmet need in lung cancer through our broad development programme.” The safety profile for Imfinzi was consistent with its known safety profile, and no new safety concerns were reported. The data will be shared at a forthcoming medical meeting. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy based on the PACIFIC Phase III trial. Imfinzi is also being investigated as monotherapy and in combinations in several other early-stage lung cancer settings, including in medically inoperable or unresected Stage I-II NSCLC (PACIFIC-4) and unresectable, Stage III NSCLC (PACIFIC-5, 8 and 9). Notes Lung cancer Each year, there are an estimated 2.4 million people diagnosed with lung cancer globally. Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. 1-2 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of patients diagnosed with NSCLC. 3-4 The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis. 5-6 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition. 7-8 The majority of patients with resectable disease eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy. 9 Only around 58% of patients with Stage IB disease will survive for five years. This decreases to 36-46% for patients with Stage II and 24% for patients with Stage IIIA disease, reflecting a high unmet medical need. 10 ADJUVANT BR.31 ADJUVANT BR.31 is a randomised, multi-centre, double-blind Phase III trial sponsored by CCTG evaluating Imfinzi in the adjuvant treatment of 1,415 patients with Stage IB (≥4cm), II or IIIA (Seventh Edition AJCC Cancer Staging Manual) NSCLC following complete tumour resection with or without adjuvant chemotherapy. AstraZeneca provided Imfinzi and support for the trial. Patients were randomised 2:1 to receive a 20mg/kgIV infusion of Imfinzi or placebo every four weeks for up to 48 weeks. The trial is being conducted at 269 centres across 19 countries and regions including in Canada, the US, Australia, Europe and Asia. The primary endpoint is DFS in patients whose tumours express PD-L1 on 25% or more tumour cells and do not have known common EGFR mutations or ALK rearrangements. Key secondary endpoints include DFS in patients whose tumours express PD-L1 on 1% or more of cells and in patients regardless of PD-L1 tumour cell expression status, overall survival and safety. DFS is defined as time from randomisation to date of first recurrence, new cancer or death from any cause and is recognised as an important clinical measure by both physicians and patients. Canadian Cancer Trials Group (CCTG) CCTG is an academic cancer clinical trials research cooperative that runs Phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From the operations centre at Queen’s University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is a national program of the Canadian Cancer Society, and their aim is to improve survival and quality of life for all people with cancer. Imfinz i 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 responses. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi also demonstrated statistically significant and clinically meaningful event-free survival results in patients with resectable early-stage NSCLC based on the AEGEAN Phase III trial. Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery is approved for patients in Switzerland based on this trial. In limited-stage SCLC, Imfinzi demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of OS and progression-free survival (PFS) compared to placebo in patients who had not progressed following standard-of-care concurrent chemoradiotherapy in the ADRIATIC Phase III trial. In addition to its indications in lung cancers, Imfinzi is 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 and in combination with chemotherapy (carboplatin plus paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient in the US. Since the first approval in May 2017, more than 220,000 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, 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 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. 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 June 2024. 2. 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 June 2024. 3. LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer . Accessed June 2024. 4. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol . 2019;26(1):37-42. 5. Cagle PT, et al . Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137(9):1191-1198. 6. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21(suppl 7):vii196-198. 7. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis . 2016:8(Suppl 6);S494-S497. 8. LUNGevity Foundation. Screening and Early Detection. Available at: https://www.lungevity.org/lung-cancer-basics/screening-early-detection . Accessed June 2024. 9. Pignon JP, et al . Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559. 10. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol . 2007;2(8):706-14. SOURCE: AstraZeneca

ImmunotherapyPhase 3Clinical ResultDrug Approval

25 Jun 2024

·pipelinereview.com

Imfinzi demonstrated statistically significant and clinically meaningful improvement in event-free survival and overall survival for muscle-invasive bladder cancer in NIAGARA Phase III trial

First immunotherapy regimen before and after surgery to extend survival in bladder cancer LONDON, UK I June 25, 2024 I Positive high-level results from the NIAGARA Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) versus neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC). Patients were treated with Imfinzi in combination with neoadjuvant chemotherapy before cystectomy (surgery to remove the bladder) followed by Imfinzi as adjuvant monotherapy. Approximately one in four patients with bladder cancer has evidence of the tumour invading the muscle wall of the bladder (without distant metastases), known as MIBC. 1,2 In the MIBC setting, approximately 117,000 patients are treated with current standard of care. 3 Standard treatment includes neoadjuvant chemotherapy and radical cystectomy. 4 However, even after cystectomy, patients experience high rates of recurrence and a poor prognosis. 4 Professor Thomas Powles, MD, Professor, Director of Barts Cancer Centre (QMUL), London, UK, and investigator in the trial, said: “Nearly half of patients with muscle-invasive bladder cancer who receive standard of care still experience disease recurrence or progression. These NIAGARA data show for the first time that adding durvalumab to chemotherapy before surgery followed by durvalumab extends patients’ lives.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The NIAGARA results support our strategy to move immunotherapy to the early stages of cancer treatment. This perioperative regimen with Imfinzi improved survival and reduced the rate at which patients experience disease recurrence or progression. We are eager to bring this regimen with the potential to transform the standard of care to patients as soon as possible.” Imfinzi was generally well-tolerated and no new safety concerns were observed in either the neoadjuvant or adjuvant setting. The safety profile of Imfinzi and neoadjuvant chemotherapy was consistent with the known profile of the individual medicines. The addition of Imfinzi did not increase the discontinuation rate due to adverse events and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Notes Muscle-invasive bladder cancer Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year. 5 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract. 6 Muscle-invasive bladder cancer, named for its growth into the muscle wall of the bladder, accounts for about a quarter of all bladder cancer cases. 1,2 Approximately 50% of patients who undergo bladder removal surgery experience disease recurrence. 4 Treatment options that prevent disease recurrence after surgery are critically needed. NIAGARA NIAGARA is a randomised, open-label, multi-centre, global Phase III trial evaluating Imfinzi as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1063 patients were randomised to receive Imfinzi plus chemotherapy or chemotherapy alone prior to cystectomy, followed by Imfinzi or no further treatment after surgery. The trial is being conducted at 192 centres across 22 countries and regions including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS, defined as the time from treatment randomisation to an event like tumour recurrence or progression and pathologic complete response. Key secondary endpoints are OS and safety. 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 responses. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage small cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi in combination with neoadjuvant platinum-containing chemotherapy before surgery and as adjuvant monotherapy after surgery has been approved in Switzerland for the treatment of adult patients with resectable NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In addition to its indications in lung cancers, Imfinzi is 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 and in combination with chemotherapy (carboplatin plus paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient in the US. Since the first approval in May 2017, more than 220,000 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, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. Imfinzi is being tested across early- and late-stage bladder cancer in various treatment combinations, including in non-muscle invasive disease (POTOMAC), patients with MIBC who are cisplatin-ineligible or refusing cisplatin (VOLGA) and locally advanced or metastatic disease (NILE). 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 as well as 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. Burger M, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol . 2013;63(2):234-241. 2. National Collaborating Centre for Cancer. Bladder Cancer: Diagnosis and Management. London: National Institute for Health and Care Excellence (NICE). Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/books/NBK356289/. Accessed June 2024. 3. Cerner CancerMPact database. Accessed June 2024. Reflects epidemiology estimates across G8 countries (US, EU, Japan, China). 4. Witjes JA, et al. EAU Guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol . 2021;1-94. 5. World Health Organization. International Agency for Research on Cancer. Bladder Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf. Accessed June 2024. 6. American Cancer Society. What Is Bladder Cancer? Available at: https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed June 2024. SOURCE: AstraZeneca

ImmunotherapyClinical ResultPhase 3Drug Approval

25 Jun 2024

·firstwordpharma.com

One hit, one miss for AstraZeneca’s Imfinzi in bladder, lung cancer studies

AstraZeneca announced Tuesday positive top-line results from a Phase III study of Imfinzi (durvalumab) plus chemotherapy, demonstrating survival gains over neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC). However, the PD-L1 inhibitor’s success was dampened by findings from another late-stage trial in early-stage non-small-cell lung cancer (NSCLC), where it failed to meet the key survival endpoint against placebo.Survival advantage in MIBCIn the Phase III NIAGARA study, 1063 patients with MIBC were randomly assigned to either Imfinzi plus chemotherapy or chemotherapy alone before undergoing cystectomy, followed by Imfinzi or no further treatment after surgery. Data showed that patients treated with Imfinzi plus chemotherapy had a significant and clinically meaningful improvement on the main goal of event-free survival (EFS) and also on the key secondary endpoint of overall survival (OS) compared with those receiving only neoadjuvant chemotherapy.According to AstraZeneca, the addition of Imfinzi did not increase the discontinuation rate due to adverse events and did not compromise patients' ability to complete surgery compared to neoadjuvant chemotherapy alone.“The NIAGARA results support our strategy to move immunotherapy to the early stages of cancer treatment,” said Susan Galbraith, EVP of oncology R&D at AstraZeneca, adding that Imfinzi has the “potential to transform the standard of care” for MIBC. The company indicated that the results will be presented at an upcoming medical meeting and submitted to regulatory authorities.Imfinzi received accelerated FDA clearance in 2017 for treating advanced bladder cancer, but this indication was voluntarily withdrawn in 2021 after a confirmatory trial failed. The drugmaker noted that Imfinzi is currently being investigated in early- and late-stage bladder cancer across multiple settings in various treatment combinations.Endpoint missed in NSCLCMeanwhile, the Phase III ADJUVANT BR.31 study enrolled 1415 patients with Stage IB, II or IIIA NSCLC having 25% or more expression of PD-L1 on tumour cells. Participants were randomised to receive either Imfinzi or placebo following resection every four weeks for up to 48 weeks. Results showed that Imfinzi did not meet the primary endpoint of disease-free survival versus placebo.Despite the unfavourable results of the study, “Imfinzi has helped change the treatment landscape and achieved multiple positive Phase III trials for patients with earlier stages of lung cancer,” Galbraith remarked. The PD-L1 inhibitor is currently approved for patients with unresectable Stage III NSCLC not having experienced disease progression following chemoradiation in the curative-intent setting, as well as for treating metastatic NSCLC in combination with AstraZeneca’s anti-CTLA-4 antibody Imjudo (tremelimumab) and chemotherapy. Imfinzi generated sales of $4.2 billion last year.

Clinical ResultPhase 3Drug ApprovalImmunotherapyAccelerated Approval

100 Deals associated with Tremelimumab

External Link

KEGG	Wiki	ATC	Drug Bank
D06657	Tremelimumab	-	DB11771

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	EU	AstraZeneca AB	20 Feb 2023
Advanced Hepatocellular Carcinoma	IS	AstraZeneca AB	20 Feb 2023
Advanced Hepatocellular Carcinoma	LI	AstraZeneca AB	20 Feb 2023
Advanced Hepatocellular Carcinoma	NO	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	EU	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	IS	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	LI	AstraZeneca AB	20 Feb 2023
metastatic non-small cell lung cancer	NO	AstraZeneca AB	20 Feb 2023
Advanced Lung Non-Small Cell Carcinoma	JP	AstraZeneca KK	23 Dec 2022
Non-Small Cell Lung Cancer	US	AstraZeneca AB	10 Nov 2022
Unresectable Hepatocellular Carcinoma	US	AstraZeneca AB	21 Oct 2022

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 3	US	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	CN	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	JP	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	BE	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	BR	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	CA	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	EG	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	FR	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	DE	AstraZeneca PLC	28 Mar 2022
Hepatocellular Carcinoma	Phase 3	IN	AstraZeneca PLC	28 Mar 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04817826 (INFINITY, ESMO_GI2024) Manual	Phase 2	Microsatellite instability-high Stomach Cancer \| Gastroesophageal junction adenocarcinoma Neoadjuvant MSI-High	33	Tremelimumab+ Durvalumab (Cohort 1)	ipwisltjvn(tnthvpqmrm) = kszjqkikmu atwwlhopsl (jktymmaohk ) View more	Positive	27 Jun 2024
				Tremelimumab + Durvalumab (Cohort 2)	ylibshaswy(mjhabmfahd) = kdapklapjy vshcpxfktu (ozhocmnauu ) View more
NCT03249142 (INEOV, ASCO2024)	Phase 1	Ovarian Cancer Neoadjuvant BRCAm	70	NACT + durvalumab	xoljkpffzq(sqtxajwktq) = pupqscsdtw iqmvpchdnz (pvvowyrist ) View more	Positive	24 May 2024
				NACT + durvalumab + tremelimumab	xoljkpffzq(sqtxajwktq) = puocrijcss iqmvpchdnz (pvvowyrist ) View more
NCT03959293 (PRODIGE 59-FFCD 1707-DURIGAST, Pubmed)	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma Second line PD-L1 CPS \| PD-L1 TPS	96	FOLFIRI plus durvalumab	cicllogeke(nhwygmjwij) = uxfivldbzg xsxgcpjzoy (orqbtpntfq, 32.3 - 57.7) View more	Negative	04 Apr 2024
				FOLFIRI plus durvalumab and tremelimumab	cicllogeke(nhwygmjwij) = qwwghajvug xsxgcpjzoy (orqbtpntfq, 42.3 - 68.3) View more
PRNewswire Manual	Phase 2	Squamous Cell Carcinoma of Head and Neck Neoadjuvant	48	durvalumab+tremelimumab	fsbylpfkjy(justnsurjq) = heddtxbtyn gpgwwjmfiq (hqpnqtdpoq ) View more	Positive	26 Mar 2024
				durvalumab	fsbylpfkjy(justnsurjq) = nvisxazxws gpgwwjmfiq (hqpnqtdpoq ) View more
NCT02735239 (LUD2015-005, CTgov)	Phase 1/2	Esophageal Carcinoma	73	Durvalumab+Oxaliplatin+Capecitabine (Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo))	pjpokcbsgr(jqsgwwkupy) = piipfrhtcd kqguwtwztt (dlwvosotpy, epobaevloj - flbsllcfah) View more	-	22 Mar 2024
				Tremelimumab+Durvalumab+Oxaliplatin+Capecitabine (Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo)	pjpokcbsgr(jqsgwwkupy) = htlhaxvjpm kqguwtwztt (dlwvosotpy, vtzsucloat - ncdhqupvlk) View more
NCT03837899 (CTgov)	Phase 1/2	Acute Lymphoblastic Leukemia \| Advanced Malignant Solid Neoplasm	56	Tremelimumab+Durvalumab (Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg)	uktpslduwz(patytbnpmw) = phzjtvxqir mxnxdybjjf (bzhbgdvbfi, uikdmoemue - dwfpdwcbsb) View more	-	19 Mar 2024
				Tremelimumab+Durvalumab (Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg)	uktpslduwz(patytbnpmw) = aubldwmbjo mxnxdybjjf (bzhbgdvbfi, eecvazpfxa - wwrakdtkvs) View more
NCT03015129 (ANZGOG1601, CTgov)	Phase 2	Uterine Carcinosarcoma \| Recurrent Endometrial Cancer	80	Durvalumab (Durvalubmab)	jevayusixh(zazlxkxdrt) = kcnkwcyief wilswmmpgq (rsezbghrfc, uidwrjsmhw - bmhlkbopdi) View more	-	06 Feb 2024
				Tremelimumab+Durvalumab (Durvalubmab + Tremelimumab)	jevayusixh(zazlxkxdrt) = dozgrdwrqp wilswmmpgq (rsezbghrfc, ozvuncafhq - rjdwfhsdtr) View more
JPRN-jRCT2031210046 (DEPARTURE, ASCO_GI2024) Manual	Phase 1	Advanced Hepatocellular Carcinoma	15	Durvalumab + Tremelimumab + Particle Therapy (Cohort A)	fjnhryhwfu(nzunjzianb) = psjwokcfrz qkipyvhzxs (rqchwbtyry ) View more	Positive	18 Jan 2024
				Durvalumab + Tremelimumab + Particle Therapy (Cohort B)	fjnhryhwfu(nzunjzianb) = hmaewiwgjp qkipyvhzxs (rqchwbtyry ) View more
POSEIDON (ESMO_IO2023)	Phase 3	First line EGFR/ALK wild-type	1,013	Durvalumab + tremelimumab + chemotherapy	unpjtfewuv(dzxkmixaeg): HR = 0.86 (95% CI, 0.72 - 1.02), P-Value = 0.0758 View more	Positive	06 Dec 2023
				Chemotherapy
NCT03298451 (HIMALAYA, AASLD2023)	Phase 3	Unresectable Hepatocellular Carcinoma	-	STRIDE (tremelimumab 300 mg + durvalumab 1500 mg)	vzrzmwazat(mdtiudmboa): P-Value = 0.78	-	10 Nov 2023
				Sorafenib (400 mg)

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis