Efficacy and Safety of Short Course Radiotherapy Combined With CAPOX and PD-1/CTLA-4 Bispecific Antibody QL1706 in Patients With Liver Metastases From Rectal Cancer

To enhance the treatment efficacy of rectal cancer liver metastasis through a multidisciplinary approach of radiotherapy, immunotherapy, and chemotherapy, and to provide a new direction for the combination treatment strategy.

Start Date01 Mar 2025

Sponsor / Collaborator

Fujian Cancer Hospital

NCT06809530

/ Not yet recruitingPhase 1/2IIT

Intrathecal Administration of Double Checkpoint Inhibition in Combination with Pemetrexed in Patients with Leptomeningeal Metastasis: a Monocentric Phase I/II

The objective of the present study is to evaluate the tolerability, feasibility, safety and therapeutic response of intrathecal administration of double checkpoint inhibition(QL1706) in combination with pemetrexed in patients with leptomeningeal metastasis.

Start Date01 Mar 2025

Sponsor / Collaborator

Guangzhou Medical University

NCT06829797

/ Not yet recruitingPhase 2IIT

A Multicenter Randomized Controlled Phase II Trial of Iparomlimab and Tuvonralimab (QL1706) Combined with SOX Chemotherapy Versus Chemotherapy Alone in the Treatment of Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma(STAR-03)

To explore the efficacy of Iparomlimab and Tuvonralimab (QL1706) in combination with SOX chemotherapy versus chemotherapy alone for the neoadjuvant treatment of locally-progressed gastric/gastroesophageal union adenocarcinomas by evaluating the complete pathologic remission rate (pCR).

Start Date28 Feb 2025

Sponsor / Collaborator

Shandong Provincial Hospital

100 Clinical Results associated with Iparomlimab/Tuvonralimab

100 Translational Medicine associated with Iparomlimab/Tuvonralimab

100 Patents (Medical) associated with Iparomlimab/Tuvonralimab

Literatures (Medical) associated with Iparomlimab/Tuvonralimab

08 May 2023·Journal of hematology & oncology

First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors.

Article

Author: Yan, Wei ; Zhu, Dongyuan ; Qu, Shenhong ; Zhang, Yiping ; Huang, Xian ; Yang, Yingying ; Zang, Aimin ; Zhang, Li ; Peng, Yufeng ; Yu, Zhuang ; Liang, Jin ; Hao, Yanrong ; Liu, Zhi ; Xue, Shilin ; Chen, Junmin ; Chen, Chuanben ; Feng, Weineng ; Liu, Baorui ; Ba, Yi ; Zhao, Yuanyuan ; Su, Wuyun ; Qu, Song ; Chen, Zhendong ; Fanslow, Bill ; Li, Qingshan ; Jin, Chuan ; Yang, Guihong ; Ma, Yuxiang ; Liu, Xianling ; Ouyang, Weiwei ; Zhang, Guoping ; Li, Yong ; Wang, Xiangcai ; He, Jianbo ; Cheng, Ying ; Kang, Xiaoyan ; Yang, Mengxiang ; Zhao, Hongyun

BACKGROUND:

QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t_1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies.

METHODS:

In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated.

RESULTS:

Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively.

CONCLUSIONS:

QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

Signal transduction and targeted therapy

QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

Article

Author: Xue, Shilin ; Zhang, Yaxiong ; Lu, Lu ; Zhao, Hongyun ; Zhang, Li ; Yang, Yunpeng ; Chen, Gang ; Zhou, Ting ; Kang, Xiaoyan ; Fang, Wenfeng ; Wu, Ting ; Zhao, Yuanyuan ; Huang, Yan ; Zhou, Ningning ; Chen, Likun

Abstract:

First-line chemoimmunotherapy (with or without bevacizumab) has improved outcomes in advanced non-small cell lung cancer (NSCLC). Here, this open-label, multi-cohort phase II study (NCT05329025) was done to investigate the safety and efficacy of QL1706 (a single bifunctional MabPair product against PD-1 and CTLA-4) and chemotherapy with or without bevacizumab in this population. Patients were enrolled into five different cohorts based on genotype (cohorts 1-4, epidermal growth factor receptor [EGFR] wild-type; cohort 5, EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors [TKIs]). Between June 11, 2021 and December 29, 2021, 91 patients were enrolled. Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia (60 [65.9%]), infusion-related reactions (48 [52.7%]), and pruritus (44 [48.4%]). Grade ≥ 3 TRAEs occurred in 30 (33.0%) patients. Twenty-seven (45%) patients with wild-type EGFR achieved partial response (PR) (objective response rate [ORR] = 45%) and had a median progression-free survival (mPFS) of 6.8 months (95% CI: 5.2-9.7). For 31 patients harboring mutated EGFR, 17 (54.8%) achieved PR (ORR = 54.8%), with an mPFS of 8.5 months (95% CI: 5.72-not evaluable). Overall, QL1706 plus chemotherapy, regardless of having bevacizumab, was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting. Moreover, QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy, demonstrating a potential for treating this population.

Frontiers in oncology

Case Report: Immune checkpoint inhibitor-related vitiligo-like depigmentation in non-melanoma advanced cancer: A report of three cases and a pooled analysis of individual patient data

Author: Wu, Longqiu ; Rao, Hui ; Wen, Xuejiao ; Huang, Li ; Guo, Zheng ; Zeng, Xiaoli

Background:

Vitiligo-like depigmentation is a common skin adverse event in patients receiving immunotherapy for malignant melanoma, but has been rarely reported in patients with non-melanoma malignancies. To better understand this immune-related adverse event, we reviewed a series of cases of immunotherapy induced vitiligo-like depigmentation in patients with cancers other than malignant melanoma.

Case presentation:

We report three cases of vitiligo-like depigmentation after immune checkpoint inhibitor treatment in gastric adenocarcinoma, lung adenocarcinoma, and squamous cell carcinoma. The first case was treated with camrelizumab, the second was treated with QL1706 injection and sintilimab, and the third was treated with tislelizumab. Pembrolizumab, nivolumab, and ipilimumab caused the majority of vitiligo-like depigmentation, and all three of our patients experienced similar vitiligo-like depigmentation after taking other immune checkpoint inhibitors.

Methods:

Three patients who presented with vitiligo-like depigmentation after treatment with immune checkpoint inhibitors were selected. The clinical features, including radiological and histological examination, and the treatment process were reviewed. Eighteen previously published cases of vitiligo-like depigmentation were also used to analyze the results. The severity of vitiligo-like depigmentation in these cases was graded according to the Common Terminology Criteria for Adverse Events, version 5.0.

Results:

Vitiligo-like depigmentation occurred in 13 men (61.90%) and 8 women (38.10%), aged from 46 to 79 years, with an average age of 69.9 years. Of the 21 reviewed cases, vitiligo-like depigmentation was described in lung cancer (13/21, 61.90%), clear cell renal cell carcinoma (2/21, 9.52%), acute myeloid leukemia (1/21, 4.76%), cholangiocarcinoma (1/21, 4.76%), urothelial carcinoma (1/21, 4.76%), oral squamous cell carcinoma (1/21, 4.76%), esophageal squamous cell carcinoma (1/21, 4.76%), and gastric adenocarcinoma (1/21, 4.76%). The severity of vitiligo-like depigmentation after immunotherapy was unrelated to sex, age, cancer type, previous autoimmune diseases, and medication.

Conclusions:

Vitiligo-like depigmentation is a non-specific skin adverse event in melanoma immunotherapy, but arises as a direct result of treatment with immune checkpoint inhibitors. Vitiligo-like depigmentation has an irregular location, is not limited to direct sunlight cracks, and has also been reported on hair on the head, eyelashes, and eyebrows. People without any skin or autoimmune diseases can also experience vitiligo-like depigmentation after immunotherapy; the incidence of which is irrespective of sex, age, cancer type, previous autoimmune diseases, and medication.

News (Medical) associated with Iparomlimab/Tuvonralimab

14 Jan 2025

·www.prnewswire.com

Non-Small Cell Lung Cancer Clinical Trial Pipeline Boom as Over 100 Companies Leading the Charge in Research and Development | DelveInsight

Advancements in targeted therapies have transformed the treatment landscape for NSCLC, enabling precision medicine approaches that improve outcomes. These therapies focus on specific genetic mutations or molecular drivers, such as EGFR, ALK, ROS1, BRAF, and MET, which are commonly implicated in NSCLC. Drugs targeting these mutations, such as tyrosine kinase inhibitors (TKIs), offer significant benefits, including higher response rates, improved progression-free survival, and fewer off-target effects compared to traditional chemotherapy. Additionally, continuous innovation has led to the development of next-generation inhibitors that overcome resistance to earlier therapies, further enhancing their efficacy. LAS VEGAS, Jan. 14, 2025 /PRNewswire/ -- DelveInsight's ' Non-Small Cell Lung Cancer Pipeline Insight 2025 ' report provides comprehensive global coverage of pipeline NSCLC therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the NSCLC pipeline domain. Key Takeaways from the Non-Small Cell Lung Cancer Pipeline Report DelveInsight's NSCLC pipeline report depicts a robust space with 100+ active players working to develop 120+ pipeline therapies for NSCLC treatment. Key NSCLC companies such as Merck Sharp & Dohme LLC, AbbVie, Qilu Pharmaceutical Co., Ltd., Suzhou Puhe Pharmaceutical Technology Co., LTD, Exelixis, Genmab, OncoResponse, Inc., Next Point Therapeutics, Inc., Light Chain Bioscience - Novimmune SA, Immunitas Therapeutics, Hansoh BioMedical R&D Company, Mythic Therapeutics, Shanghai Henlius Biotech, and others are evaluating new NSCLC drugs to improve the treatment landscape. Promising NSCLC pipeline therapies such as V940, Telisotuzumab Vedotin, QL1706, YK-029A, XL092, PRO1184, OR2805, NPX267, NI-1801, IMT-009, HS-20117, MYTX-011, HLX301, and others are under different phases of NSCLC clinical trials. In December 2024, the FDA granted breakthrough therapy designation to sacituzumab tirumotecan (MK-2870/SKB264/) for the treatment of patients with advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC). In September 2024, AbbVie announced that it had submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for accelerated approval of elotuzumab vedotin (Teliso-V) in adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with c-Met protein overexpression. In August 2024, the FDA granted Fast track designation to Deltacel (KB-GDT-01) with low-dose radiation therapy to potentially treat patients with metastatic non–small cell lung cancer (NSCLC) whose disease progressed on 2 or more prior lines of standard-of-care therapy, including immune checkpoint inhibitors, platinum-based chemotherapy, and targeted therapy. In July 2024, Nuvalent announced the first patient dosed in HEROEX-1 Phase Ia/Ib clinical trial of NVL-330, its novel HER2-selective Inhibitor. In April 2024, ABVC BioPharma announced that the Company and its affiliate Rgene Corporation entered into a comprehensive licensing agreement with OncoX for the drug ABV-1501. Under the terms of the agreement, ABVC grants OncoX exclusive rights for one of ABVC's four products in its Oncology pipeline to develop, manufacture, and commercialize BLEX 404. In April 2024, Hansoh Pharma announced that the Class 1 new drug " HS-10504 tablet" independently developed by its subsidiary Jiangsu Hansoh Pharmaceutical Group Co., Ltd. and Shanghai Hansoh Biomedical Technology Co., Ltd. had obtained the clinical trial notification letter issued by the National Medical Products Administration of the People's Republic of China. It is intended for the treatment of advanced non-small cell lung cancer, with specific indications to be determined after clinical trials. In February 2024, the FDA granted breakthrough therapy designation to NVL-520 as a treatment for patients with ROS1-positive metastatic non–small cell lung cancer (NSCLC) who received prior treatment with at least 2 ROS1 tyrosine kinase inhibitors (TKIs). Request a sample and discover the recent advances in NSCLC treatment drugs @ Non-Small Cell Lung Cancer Pipeline Report The NSCLC pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage NSCLC drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the NSCLC clinical trial landscape. Non-Small Cell Lung Cancer Overview Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, originating in the tissues of the lungs. Unlike small cell lung cancer, which grows rapidly, NSCLC typically develops more slowly but often spreads to other parts of the body by the time it is diagnosed, emphasizing the need for early detection and treatment. Small-cell lung cancer derives its name from the small, round appearance of its cells under a microscope, while the cells in NSCLC are larger. Despite its slower growth, NSCLC is frequently diagnosed at an advanced stage, further underscoring the importance of early intervention. In the United States, approximately 230,000 people are diagnosed with lung cancer annually, and it accounts for an estimated 135,000 deaths each year. Lung cancer causes more deaths than prostate, breast, brain, and colorectal cancers combined. It is the leading cause of cancer deaths in men and the second most common in women. However, these figures are declining, largely due to anti-smoking initiatives and reduced tobacco use. The classification of lung tumors is based on the 2015 World Health Organization (WHO) guidelines, which utilize immunohistochemistry and light microscopy to guide treatment decisions and predict outcomes. NSCLC encompasses several subtypes, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma, the most common subtype, accounts for nearly half of all lung cancer cases. Squamous cell carcinoma, once the most prevalent, typically originates in the tracheobronchial tree but is now more frequently found in peripheral lung areas. Large cell carcinoma is a diagnosis of exclusion, characterized by poor differentiation and lack of specific classification through immunohistochemistry or electron microscopy. The causes of NSCLC can be divided into avoidable and unavoidable risk factors. Tobacco use remains the most significant preventable risk factor, while other causes include alcohol consumption, exposure to secondhand smoke, asbestos, radon, arsenic, chromium, nickel, ionizing radiation, and polycyclic aromatic hydrocarbons. Diagnosis involves a comprehensive blood count (CBC), a complete metabolic panel (CMP), and imaging studies. Hypercalcemia or elevated alkaline phosphatase may indicate metastasis to bones. Initial imaging with a chest X-ray can help identify nonspecific signs, followed by computed tomography (CT) for detailed characterization. A tissue biopsy is essential for confirming the diagnosis through histopathologic and immunohistochemistry evaluation. Treatment options for NSCLC include standard therapies like surgery, radiation, chemotherapy, targeted therapy, and immunotherapy, as well as newer approaches like laser therapy, photodynamic therapy (PDT), and cryosurgery. The choice of treatment depends on the cancer's stage, the patient's functional status, comorbidities, and the molecular characteristics of the tumor. Surgery is often required for localized cases, while advanced stages may call for a combination of therapies. Participation in clinical trials can also offer access to emerging treatments. Managing NSCLC requires a collaborative, interprofessional approach, beginning with prevention. Primary care providers play a critical role in smoking cessation counseling and early detection through lung cancer screening, which can improve prognosis by identifying the disease before it progresses to advanced stages. Find out more about NSCLC treatment drugs @ Drugs for Non-Small Cell Lung Cancer Treatment A snapshot of the Non-Small Cell Lung Cancer Pipeline Drugs mentioned in the report: Learn more about the emerging NSCLC pipeline therapies @ Non-Small Cell Lung Cancer Clinical Trials Non-Small Cell Lung Cancer Therapeutics Assessment The NSCLC pipeline report proffers an integral view of the NSCLC emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Non-Small Cell Lung Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Immunostimulants, Antibody-dependent cell cytotoxicity, Cytotoxic T-lymphocyte antigen 4 inhibitors, Programmed cell death 1 receptor antagonists, T lymphocyte stimulants, Apoptosis stimulants, Mitosis inhibitors, Tubulin inhibitors, Tubulin polymerization inhibitors, Epidermal growth factor receptor antagonists, Proto-oncogene protein c-met inhibitors Key Non-Small Cell Lung Cancer Companies: Merck Sharp & Dohme LLC, AbbVie, Qilu Pharmaceutical Co., Ltd., Suzhou Puhe Pharmaceutical Technology Co., LTD, Exelixis, Genmab, OncoResponse, Inc., Next Point Therapeutics, Inc., Light Chain Bioscience - Novimmune SA, Immunitas Therapeutics, Hansoh BioMedical R&D Company, Mythic Therapeutics, Shanghai Henlius Biotech, and others Key Non-Small Cell Lung Cancer Pipeline Therapies: V940, Telisotuzumab Vedotin, QL1706, YK-029A, XL092, PRO1184, OR2805, NPX267, NI-1801, IMT-009, HS-20117, MYTX-011, HLX301, and others Dive deep into rich insights for new drugs for NSCLC treatment, visit @ Non-Small Cell Lung Cancer Drugs Table of Contents For further information on the NSCLC pipeline therapeutics, reach out @ Non-Small Cell Lung Cancer Treatment Drugs Related Reports Non-Small Cell Lung Cancer Market Non-Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key NSCLC companies including EMD Serono, Merck, Cellular Biomedicine Group, Inc., Celgene, CellSight Technologies, Inc., BeyondSpring Pharmaceuticals Inc., J Ints Bio, Forward Pharmaceuticals Co., Ltd., AstraZeneca, Bristol-Myers Squibb, Teligene US, Rain Oncology Inc, ReHeva Biosciences, Inc., Amgen, Novartis, RedCloud Bio, Parexel, Vitrac Therapeutics, LLC, Mythic Therapeutics, Instil Bio, Mirati Therapeutics Inc., Daiichi Sankyo, Inc., AstraZeneca, Precision Biologics, Inc, Promontory Therapeutics Inc., Palobiofarma SL, Regeneron Pharmaceuticals, Revolution Medicines, Inc., Cullinan Oncology, LLC, Iovance Biotherapeutics, Inc., Innate Pharma, among others. HER2-mutant Non-Small Cell Lung Cancer Pipeline HER2-mutant Non-Small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key HER2-mutant non-small cell lung cancer companies, including Dizal Pharmaceuticals, Puma Biotechnology, AstraZeneca, Jiangsu Hengrui Medicine, among others. Small Cell Lung Cancer Market Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key advanced small cell lung cancer companies, including Ascentage Pharma, Merck & Co, AstraZeneca, Advenchen Laboratories, Advanced Accelerator Applications, Trillium Therapeutics, Wigen Biomedicine, Linton Pharm, Carrick Therapeutics, among others. Small-cell Lung Cancer Pipeline Small-cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key small-cell lung cancer companies, including Ascentage Pharma, Merck & Co, AstraZeneca, Advenchen Laboratories, GlaxoSmithKline, Advanced Accelerator Applications, Trillium Therapeutics, Vernalis, Oncoceutics, NewBio Therapeutics, Wigen Biomedicine, Linton Pharm, Carrick Therapeutics, Xencor, Jiangsu HengRui Medicine, Aileron Therapeutics, Roche, Ipsen, Celgene, Lee's Pharmaceutical Limited, AbbVie, G1 Therapeutics, Chipscreen Biosciences, Luye Pharma Group, Shanghai Henlius Biotech, CSPC ZhongQi Pharmaceutical Technology, Impact Therapeutics, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/in

15 Mar 2024

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Qilu Pharmaceutical Showcases QL1706 Clinical Trial Outcomes in Oral Presentation at ESGO 2024

JINAN, China, March 15, 2024 /PRNewswire/ -- On 8 March local time, during the 25th European Society of Gynecological Oncology (ESGO) Conference (ESGO 2024) in Spain, Qilu Pharmaceutical unveiled the Phase II clinical trial results for iparomlimab and tuvonralimab (QL1706) in an oral presentation. This trial, known as DUBHE-C-206, recruited patients with recurrent or metastatic cervical cancer who failed first-line standard treatments. The findings were presented by Professor Jihong Liu from the Sun Yat-sen University Cancer Center in China. Study Background and Design Cervical cancer is one of the most prevalent malignancies among women and a leading cause of cancer-related death. For those who have failed the first-line standard therapy, the currently available treatment options are inadequate. The objective response rate (ORR) for pembrolizumab was 12.2%, with an ORR of 0% in the PD-L1-negative population[1]. Additionally, the median progression-free survival (PFS) and median overall survival (OS) were reported to be 2.1 months and 9.4 months, respectively. Similarly, cemiplimab showed an ORR of 16.4%, with a median PFS of 2.8 months and a median OS of 12.0 months[2]. This highlights the unmet need for effective and safe clinical treatments for patients with cervical cancer who failed first-line therapy. By targeting and inhibiting two immune checkpoint pathways (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), Qilu Pharmaceutical's proprietary drug QL1706 has shown a favorable safety profile and preliminary efficacy in patients with cervical cancer in early studies. The DUBHE-C-206 study aimed to evaluate the efficacy and safety of QL1706 in patients with recurrent or metastatic cervical cancer. This study was a multi-center, single-arm, open-label phase II clinical trial which enrolled patients with recurrent or metastatic cervical cancer who failed first-line platinum-based chemotherapy (with or without bevacizumab) and without prior immunotherapy. Participants received QL1706 at a dose of 5.0 mg/kg once every three weeks (Q3W). The primary endpoint of the trial was the ORR as assessed by an Independent Evaluation Committee (IRC). Secondary endpoints included the ORR as evaluated by investigators, duration of response (DoR) and disease control rate (DCR) as assessed by both IRC and investigators, PFS, 6-month and 12-month PFS rates, OS, 12-month OS rate, as well as safety, pharmacokinetics, and immunogenicity. Study Results As of April 28, 2023, the study had enrolled 148 patients with a median age of 53.0 years, including 132 (89.2%) diagnosed with squamous cell carcinoma. Of these participants, 109 (73.6%) had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 1. Additionally, 105 (70.9%) patients had a combined positive score (CPS) of ≥1, while 43 (29.1%) had a CPS of <1. Notably, 39.9% of the participants had been treated with bevacizumab, and 37.2% had received second-line and subsequent therapy. The median follow-up duration of the study was 11.0 months. In terms of efficacy, the ORR as assessed by IRC was 33.8% (95% CI: 26.2%-42.0%), and the DCR reached 64.9% (95% CI: 56.6%-72.5%). The median PFS was 5.4 months (95% CI: 3.9-6.9), with 6-month and 12-month PFS rates of 45.0% and 16.1%, respectively. The median OS had not been reached, with 6-month and 12-month OS rates standing at 83.9% and 65.4%, respectively. In subgroup analyses, the ORR for patients with a CPS of ≥1 was 37.1%, compared to 25.6% for those with a CPS of <1. Furthermore, the ORR for patients who had previously received bevacizumab was 28.8%, whereas it was 37.1% for those who had not undergone such treatment. Regarding safety, among all the participants, 104 (70.3%) experienced treatment-related adverse events (TRAEs), with the most common being hypothyroidism (20.9%) and hyperthyroidism (18.9%). TRAEs of grade 3 or higher were observed in 36 individuals (24.3%), with anemia (4.1%), increased gamma-glutamyl transferase (GGT) (2.7%), and increased lipase level (2.7%) being the most frequently reported. Three patients (2.0%) discontinued treatment due to TRAEs. There were no reported deaths resulting from TRAEs. In the study, 65 participants (43.9%) experienced immune-related adverse events (irAEs), with grade 3 or higher irAEs reported in 21 (14.2%). In conclusion, QL1706 has shown promising efficacy and acceptable safety profile in patients with recurrent or metastatic cervical cancer who failed first-line standard therapy, regardless of their PD-L1 expression. This positions QL1706 as a more effective and safer therapeutic option for patients with cervical cancer whose disease progressed after first-line standard therapy. A phase III clinical trial is currently in progress, evaluating the use of QL1706 in combination with chemotherapy (with or without bevacizumab) as a first-line treatment option. Prof. Liu from the Sun Yat-sen University Cancer Center commented, "The findings from the DUBHE-C-206 study offer new evidence to support the use of dual immunotherapy in the second- and late-line treatment of recurrent or metastatic advanced cervical cancer (ACC). They also affirm QL1706's potential as a promising new treatment option for ACC patients. The study's results have shown the efficacy benefits of QL1706 across the whole ACC patient population while demonstrating its considerable safety advantages. These findings suggest that QL1706 has the potential to significantly enhance the quality of life for patients and provide superior clinical benefits. We eagerly anticipate the outcomes of the Phase 3 trial for QL1706, which is now in progress to assess the efficacy and safety of QL1706 in combination with chemotherapy, with or without bevacizumab, as a first-line treatment for recurrent or metastatic ACC." Professor Hanmei Lou from Zhejiang Cancer Hospital stated, "For ACC patients who have failed first-line therapy, the available treatment options are still limited and exhibit unsatisfactory efficacy, highlighting substantial unmet clinical needs. The efficacy and safety data from the DUBHE-C-206 study are promising. Compared with the previously reported combination therapy involving PD-1 and CTLA-4 inhibitors, QL1706 has demonstrated reduced toxicity and offers notable advantages in both safety and efficacy. This further supports the use of dual immunotherapy for the treatment of recurrent or metastatic ACC. Consequently, the data from the DUBHE-C-206 study holds significant clinical value and implications." Ms Xiaoyan Kang, Executive Deputy General Manager of Qilu Pharmaceutical's Clinical Research & Development Center and Chief Medical Officer (CMO) for Oncology, explained, "QL1706 represents the world's first dual-functional MabPair antibody targeting both PD-1 and CTLA-4 pathways. Data from several clinical studies of this novel drug have been released. The inclusion of the latest clinical trial results in the oral presentation at the ESGO conference underscores the international academic community's interest in and recognition of the clinical potential of this novel product. Currently, multiple Phase III clinical trials involving QL1706 are in progress, covering various disease indications. Going forward, we plan to further accelerate the clinical development of QL1706 to ensure that this treatment can reach and benefit patients as soon as possible." References: 1. J Clin Oncol. 2019;37(17):1470-1478. 2. N Engl J Med. 2022;386(6):544-555. SOURCE Qilu Pharmaceutical Co., Ltd.

Clinical ResultPhase 2ImmunotherapyPhase 3ASCO

06 Mar 2024

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Non-Small-Cell Lung Cancer (NSCLC) Pipeline Landscape Report 2024: Comprehensive Insights About 100+ Companies and 120+ Pipeline Drugs - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Non-Small-Cell Lung cancer (NSCLC) - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 100+ companies and 120+ pipeline drugs in Non-Small-Cell Lung cancer (NSCLC) pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The reportoutlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Non-Small-Cell Lung cancer (NSCLC) pipeline landscape is provided which includes the disease overview and Non-Small-Cell Lung cancer (NSCLC) treatment guidelines. The assessment part of the report embraces, in depth Non-Small-Cell Lung cancer (NSCLC) commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Non-Small-Cell Lung cancer (NSCLC) collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Non-Small-Cell Lung cancer (NSCLC) R&D. The therapies under development are focused on novel approaches to treat/improve Non-Small-Cell Lung cancer (NSCLC) . Non-Small-Cell Lung cancer (NSCLC) Emerging Drugs Chapters This segment of the Non-Small-Cell Lung cancer (NSCLC) report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Non-Small-Cell Lung cancer (NSCLC) Emerging Drugs V940: Merck Sharp & Dohme LLC V940 is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient's tumor. It is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. The drug is in Phase III stage for the treatment of NSCLC. QL1706: Qilu Pharmaceutical Co., Ltd. QL1706 is an investigational bifunctional antibody with additional anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody could increase the anti-tumor effect of anti-programmed cell death 1 (PD-1) antibody. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies produced by a single cell line. The drug is in Phase III stage for the treatment of NSCLC. Zenocutuzumab (MCLA-128): Merus N.V. Zenocutuzumab (MCLA-128; Zeno) is a Biclonics antibody that overcomes HER3 mediated NRG1 (or NRG1 fusion) signaling in tumor cells. Zeno docks on HER2, then binds to and blocks the NRG1 fusion-HER3 interaction and HER3 heterodimerization with HER2. It has a dual mechanism against cancer, as it prevents NRG1 fusions from binding to the protein HER3 and it blocks the interaction of HER3 with HER2, which the cancer cells depend on to survive and multiply. Currently, the drug is in Phase II stage for the treatment of NSCLC. ZW49: Zymeworks BC Inc. ZW49 (zanidatamab zovodotin) is a bispecific anti-HER2 ADC that is based on the same antibody framework as ZW25 but armed with a cytotoxic payload. A biparatopic (targeting two different non-overlapping epitopes on ERBB2, on extracellular domains 2 (ECD2) and 4 (ECD4). ZW25 is an anti-HER2 biparatopic antibody which binds to the same domains as trastuzumab and pertuzumab. ZW25 simultaneously binds two distinct sites on HER2, a protein expressed on many types of cancer cells. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, increased antibody binding, receptor clustering, and removal of HER2 from the cell surface, and potent e?ector function. ZW49 is in Phase I of clinical trials for the treatment of non-small cell lung cancer. Non-Small-Cell Lung cancer (NSCLC): Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Non-Small-Cell Lung cancer (NSCLC) therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Non-Small-Cell Lung cancer (NSCLC) drugs. Non-Small-Cell Lung cancer (NSCLC) : Therapeutic Assessment Major Players in Non-Small-Cell Lung cancer (NSCLC) There are approx. 100+ key companies which are developing the therapies for Non-Small-Cell Lung cancer (NSCLC). The companies which have their Non-Small-Cell Lung cancer (NSCLC) drug candidates in the most advanced stage, i.e. Phase III include, Merck Sharp & Dohme LLC. Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Non-Small-Cell Lung cancer (NSCLC) Report Insights Non-Small-Cell Lung cancer (NSCLC) Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Non-Small-Cell Lung cancer (NSCLC) Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Merck Sharp & Dohme LLC Suzhou Puhe Pharmaceutical Technology Co., LTD Merus N.V. Zymeworks BC Inc. Cytos Biotechnology Exelixis ProfoundBio US Co. Beijing Pearl Biotechnology Limited Liability Company Pfizer OncoResponse, Inc. Next Point Therapeutics, Inc. Light Chain Bioscience - Novimmune SA Medolution Ltd. Immunitas Therapeutics Shanghai Henlius Biotech Key Products V940 YK-029A Zenocutuzumab (MCLA-128) ZW49 CMP 001 XL092 PRO1184 PLB1001 PF-07257876 OR2805 NPX267 NI-1801 Keynatinib IMT-009 HLX301 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/w14gce About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Phase 1ImmunotherapyPhase 2Phase 3ASCO

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Indication	Country/Location	Organization	Date
Metastatic Cervical Carcinoma	CN	Qilu Pharmaceutical Co., Ltd.	26 Sep 2024
Recurrent Cervical Cancer	CN	Qilu Pharmaceutical Co., Ltd.	26 Sep 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Small cell lung cancer limited stage	Phase 3	-	Qilu Pharmaceutical Co., Ltd.	01 Feb 2025
Nasopharyngeal Carcinoma	Phase 3	CN	Qilu Pharmaceutical Co., Ltd.	19 Dec 2024
Mismatch repair-deficient Colonic Cancer	Phase 3	CN	Qilu Pharmaceutical Co., Ltd.	12 Dec 2024
Advanced Hepatocellular Carcinoma	Phase 3	CN	Qilu Pharmaceutical Co., Ltd.	07 Aug 2023
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 3	CN	Qilu Pharmaceutical Co., Ltd.	10 Feb 2023
metastatic non-small cell lung cancer	Phase 3	CN	Qilu Pharmaceutical Co., Ltd.	10 Feb 2023
Non-squamous non-small cell lung cancer	Phase 3	-	Qilu Pharmaceutical Co., Ltd.	01 Feb 2023
Non-small cell lung cancer stage IIIB	Phase 3	CN	Qilu Pharmaceutical Co., Ltd.	08 Dec 2022
Esophageal Squamous Cell Carcinoma	Phase 2	CN	Qilu Pharmaceutical Co., Ltd.	19 Feb 2025
Endometrial Carcinoma	Phase 2	CN	Qilu Pharmaceutical Co., Ltd.	01 Feb 2025

Clinical Result

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Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05179317 (DUBHE-C-204, ESMO_ASIA2024) Manual	Phase 2	Uterine Cervical Cancer	60	QL1706 + paclitaxel + cisplatin/carboplatin +/- bevacizumab (without bevacizumab)	nnfklrewgy(rdnygcdzmc) = daymvkreky jucdptfyyf (gqwamfwwae ) View more	Positive	09 Dec 2024
				QL1706 + paclitaxel + cisplatin/carboplatin +/- bevacizumab (with bevacizumab)	jvyusgcvpc(rsyopamtla) = ayffrdkjwh cekjpodcqc (vddvarqdri ) View more
NCT05329025 (DUBHE-L-201, ESMO_ASIA2024) Manual	Phase 2	EGFR-mutated non-small Cell Lung Cancer EGFR Mutation	31	QL1706 (5 mg/kg) + Carboplatin + Pemetrexed + Bevacizumab	brkxpgekto(ixcganvqin) = lnntvddxkp ztaglkzsgd (qowqctvztp, 36.0 - 72.7) View more	Positive	07 Dec 2024
NCT05799820 (ESMO_ASIA2024) Manual	Phase 2	Metastatic Colorectal Carcinoma First line MSI-Low \| Microsatellite Stable (MSS) \| MSI-High	59	QL1706 5 mg/kg (MSI-high)	erdrfqxlay(soyfdwzltc) = vmbfocbqcc ciqauhahvk (ixrdjgeezv ) View more	Positive	07 Dec 2024
				QL1706 5 mg/kg + Bevacizumab + Oxaliplatin + Capecitabine (MSS/MSI-low and wild-type RAS/BRAF)	erdrfqxlay(soyfdwzltc) = akialanvmg ciqauhahvk (ixrdjgeezv, 56.2 - 82.5) View more
NCT05490719 (ESMO2024) Manual	Phase 2	Locally Advanced Esophageal Squamous Cell Carcinoma First line PD-L1-positive	39	Paclitaxel, CisplatinQL170606	zlawywmxrx(srfmelvbqx) = afqttburoh ivsnllrigo (taqnhtflgh ) View more	Positive	16 Sep 2024
				Paclitaxel+Cisplatin+QL1706 (PD-L1–positive (TPS ≥ 5%))	-
NCT05976568 (DUBHE-H-308, NEWS) Manual	Phase 2/3	Advanced Hepatocellular Carcinoma First line	-	QL1706 + Bevacizumab + chemotherapy	ijirjpzend(mdhnrcpggt) = aailqypkxx zsttsqjkll (cacamtzjiv ) View more	Positive	13 Sep 2024
				QL1706 + Bevacizumab	ijirjpzend(mdhnrcpggt) = rxpzqfydct zsttsqjkll (cacamtzjiv ) View more
NCT05976568 (DUBHE-H-308, ESMO2024) Manual	Phase 2/3	Advanced Hepatocellular Carcinoma First line	120	QL1706+bev+chemo	drfuvwvfuo(xkiwnqfnmn) = vmrgyzmjbg pgznqdiiww (vrwznibfgt, 19.2 - 54.6) View more	Positive	13 Sep 2024
				QL1706+bev	drfuvwvfuo(xkiwnqfnmn) = vfxsibgsxz pgznqdiiww (vrwznibfgt, 19.9 - 56.1) View more
NCT05557565 (DUBHE-C-206, ESGO2024) Manual	Phase 2	Uterine Cervical Cancer Second line	148	QL1706	hwamqhwuro(mejbawbdkw) = yvhxmfapat tveqrwcskv (jqpakmlmpd, 26.2 - 42.0) View more	Positive	08 Mar 2024
NCT05329025 (Literature) Manual	Phase 2	Advanced Lung Non-Small Cell Carcinoma First line	91	QL1706+paclitaxel+carboplatin (Squamous non-small cell lung cancer + Cohort 1)	puwghvopmd(utmgghvasw) = Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia (60 [65.9%]), infusion-related reactions (48 [52.7%]), and pruritus (44 [48.4%]). pdnqcmwdlm (zxgfuvcfmq ) View more	Positive	29 Jan 2024
				QL1706+paclitaxel+carboplatin (Squamous non-small cell lung cancer + Cohort 2)
NCT05179317 (ESMO2023 \| PRNewswire) Manual	Phase 2	Metastatic Carcinoma to the Uterine Cervix First line	60	QL1706+paclitaxel+cisplatin/carboplatin	ntyucwgbis(srepoahzdt) = hsdurbzvtp rfneslsfqb (okwagcsgzf ) View more	Positive	22 Oct 2023
				overall	ntyucwgbis(srepoahzdt) = fchxpjlami rfneslsfqb (okwagcsgzf, 9.2 - NE) View more
NCT05603039 (ASCO 12023 \| ASCO 22023) Manual	Phase 1/2	Advanced Hepatocellular Carcinoma First line	76	Bevacizumab+QL 1706	lpatixfums(mlokqfyohp) = xdgflhebqr mfzrtuuesg (vaqlatqwqx ) View more	Positive	26 May 2023
				Bevacizumab+QL 1604	lpatixfums(mlokqfyohp) = fgmjlpileh mfzrtuuesg (vaqlatqwqx ) View more

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