A Phase 1/2 Open-label Rolling-arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02A

Substudy 02A is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study.
The goal of substudy 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.

Start Date26 Jun 2020

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT03516981

/ Active, not recruitingPhase 2

A Phase 2 Precision Oncology Study of Biomarker-Directed, Pembrolizumab-(MK-3475, SCH 900475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (KEYNOTE-495; KeyImPaCT)

This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile [GEP] and tumor mutational burden [TMB]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.

Start Date01 Oct 2018

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT03179436

/ CompletedPhase 1/2

A Phase 1 / 2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.

Start Date02 Jul 2017

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Quavonlimab

100 Translational Medicine associated with Quavonlimab

100 Patents (Medical) associated with Quavonlimab

Literatures (Medical) associated with Quavonlimab

01 Dec 2023·Future oncology (London, England)

LITESPARK-012: Pembrolizumab Plus Lenvatinib With or Without Belzutifan or Quavonlimab for Advanced Renal Cell Carcinoma

Review

Author: Perini, Rodolfo F ; Powles, Thomas ; Rini, Brian I ; Voss, Martin H ; Gurney, Howard ; Rodriguez-Lopez, Karla ; Song, Yue ; Plimack, Elizabeth R ; Choueiri, Toni K

Combination treatment with immunotherapy agents and/or vascular endothelial growth factor tyrosine kinase inhibitors are a standard of care for patients with advanced clear cell renal cell carcinoma (ccRCC). Novel therapeutic combinations that include the hypoxia-inducible factor 2α inhibitor belzutifan and the cytotoxic T-lymphocyte-associated protein 4 inhibitor quavonlimab are being investigated for their potential to further improve patient outcomes. This protocol describes the rationale and design of the randomized, phase III LITESPARK-012 study, which will evaluate the efficacy and safety of pembrolizumab plus lenvatinib with or without belzutifan or quavonlimab as first-line treatment for advanced ccRCC. Results from this study may support triplet combination therapies as a potential new standard of care for advanced ccRCC. Clinical trial registry: NCT04736706 (ClinicalTrials.gov).

01 Jul 2023·Nature medicineQ1 · MEDICINE

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results.

Q1 · MEDICINE

Article

Author: Snyder, Alexandra ; Yuan, Jianda ; Gutierrez, Martin ; Palcza, John ; Kobie, Julie ; Luft, Alexander ; Felip, Enriqueta ; Tan, Daniel Shao Weng ; Hellmann, Matthew D ; Cristescu, Razvan ; Landers, Gregory A ; Basso, Andrea ; Herbst, Roy S ; Ahn, Myung-Ju ; Gubens, Matthew A ; Ma, Hua ; Lee, Jong-Seok ; Finocchiaro, Giovanna ; Lam, Wei-Sen ; Chiu, Joanne W Y ; Fong, Lawrence ; Garon, Edward B ; Yang, James Chih-Hsin ; Aggarwal, Charu

Although pembrolizumab confers clinical benefit in non-small cell lung cancer (NSCLC), only a subset of patients will respond due to a heterogenous tumor microenvironment. KEYNOTE-495/KeyImPaCT is an ongoing biomarker-directed, adaptively randomized phase 2 study investigating first-line pembrolizumab (200 mg every 3 weeks) + lenvatinib (20 mg daily), anti-CTLA-4 quavonlimab (25 mg every 6 weeks) or anti-LAG-3 favezelimab (200 mg or 800 mg every 3 weeks) in advanced NSCLC. Patients were categorized by T-cell-inflamed gene expression profile (Tcell_infGEP) and tumor mutational burden (TMB) status and randomly assigned 1:1:1 to receive pembrolizumab + lenvatinib, pembrolizumab + quavonlimab or pembrolizumab + favezelimab. The primary outcome was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 using pre-specified efficacy thresholds for each biomarker-defined subgroup (>5% (Tcell_infGEP^lowTMB^non-high (group I)), >20% (Tcell_infGEP^lowTMB^high (group II) and Tcell_infGEP^non-lowTMB^non-high (group III)) and >45% (Tcell_infGEP^non-lowTMB^high (group IV))). Secondary outcomes were progression-free survival, overall survival and safety. At data cutoff, ORR ranges were 0-12.0% in group I, 27.3-33.3% in group II, 13.6-40.9% in group III and 50.0-60.0% in group IV. ORR with pembrolizumab + lenvatinib in group III met the pre-specified efficacy threshold. The safety profile of each treatment arm was consistent with the known safety profile of each combination. These data demonstrate the feasibility of prospective Tcell_infGEP and TMB assessment to study the clinical activity of first-line pembrolizumab-based combination therapies in advanced NSCLC. ClinicalTrials.gov registration: NCT03516981 .

01 Sep 2021·LUNG CANCERQ2 · MEDICINE

Anti–cytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer

Q2 · MEDICINE

Article

Author: Yixin Ren ; Myung-Ju Ahn ; Dong-Wan Kim ; Dusan Kotasek ; Shabana Siddiqi ; Drew Rasco ; Ruth Perets ; Adnan Nagrial ; Dae Ho Lee ; Jair Bar ; Martin Gutierrez ; Byoung Chul Cho ; David R. Spigel ; Rachel A. Altura ; Kiyotaka Yoh ; Jiaxin Niu ; Corinne Maurice-Dror ; Miyako Satouchi

OBJECTIVES:

This first-in-human phase I study (NCT03179436) investigated anti-cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody quavonlimab and anti-programmed death 1 monoclonal antibody pembrolizumab in patients with advanced solid tumors. The study was conducted in two parts: dose-escalation (part 1) and dose-confirmation (part 2). First-line treatment with quavonlimab + pembrolizumab conferred encouraging antitumor activity (objective response rate [ORR], 28%-40%) and was generally well tolerated (grade ≥ 3 treatment-related adverse events [TRAEs] were lowest with quavonlimab 25 mg every 6 weeks [Q6W] at 30% and highest with quavonlimab 75 mg Q3W at 57%) in non-small cell lung cancer. We present data from patients with extensive-stage small cell lung cancer (SCLC) receiving second-line or later therapy.

MATERIALS AND METHODS:

Patients with stage III/IV SCLC received quavonlimab 75 mg Q6W plus pembrolizumab 200 mg Q3W for ≤ 2 years. Primary endpoints were safety and tolerability; ORRs as assessed by blinded independent central review per Response Evaluation Criteria In Solid Tumorsv1.1 was a secondary endpoint. Progression-free survival (PFS), overall survival (OS), and the correlation of response with PD-L1 expression were exploratory endpoints.

RESULTS:

Forty patients with extensive-stage SCLC received treatment; median follow-up was 13 months. Dose-limiting toxicity occurred in 4 patients (10%). TRAEs occurred in 80% of patients; grade 3 events occurred in 33% of patients and no grade 4/5 events were reported. Confirmed ORRs (95% CI) were 18% (7-33) among all patients, 7% (<1-34) for PD-L1-positive tumors (n = 14), and 19% (5-42) for PD-L1-negative tumors (n = 21). Response duration ranged from 2.9 to 19.1+ months. Median PFS was 2.0 months; 6-month PFS rate was 26%. Median OS was 11.0 months; 6-month OS rate was 66%.

CONCLUSIONS:

Encouraging antitumor activity was observed with quavonlimab + pembrolizumab in patients with extensive-stage SCLC; responses were observed in PD-L1-positive and PD-L1-negative tumors. The combination was tolerable with manageable toxicities.

News (Medical) associated with Quavonlimab

18 Feb 2025

·www.fiercepharma.com

As BMS-paired triplet misses survival mark in kidney cancer, Exelixis shifts focus elsewhere

Exelixis has projected Cabometyx revenue of $3 billion in 2030 and has said that its follow-on TKI, zanzalintinib, could reach $5 billion in 2033 revenue. Newly published detailed clinical trial data show why Exelixis abandoned a plan to seek an FDA approval for a combination of its Cabometyx and Bristol Myers Squibb’s Opdivo and Yervoy in kidney cancer.Adding Cabometyx to Opdivo and Yervoy failed to improve patients’ life expectancy in previously untreated, intermediate- or poor-risk advanced renal cell carcinoma, according to the final results from the phase 3 COSMIC-313 trial.Instead, the overall survival data slightly favored the doublet. Patients who received the Cabometyx-containing triplet lived a median 41.9 months, versus 42 months for Opdivo-Yervoy alone. The triplet was linked to a marginal 2% higher risk of death, according to data presented at the ASCO Genitourinary Cancers Symposium.When disclosing the overall survival miss in August, Exelixis’ chief medical officer, Amy Peterson, M.D., said the company did not plan to file the study with regulators for a possible label expansion.Several years ago, the Cabometyx-Opdivo-Yervoy combo showed it could reduce the risk of disease progression or death by 27% compared with Opdivo and Yervoy alone. The magnitude of that progression-free survival benefit, though statistically significant, was deemed weak, and the FDA requested to see more mature overall survival results to consider a filing.“We just didn’t see a risk-benefit profile going forward that was really going to raise the bar relative to the current combinations,” Exelixis’ commercial chief P.J. Haley said of the final COSMIC-313 readout on a conference call in August. It’s not the end of the world for Exelixis because the existing combination of Cabometyx and Opdivo has been the leading tyrosine kinase inhibitor (TKI)-plus-immunotherapy regimen in the competitive first-line kidney cancer field. However, the COSMIC-313 flop means the company missed an opportunity to take more market share.Meanwhile, for Cabometyx, Exelixis is focused on an upcoming FDA decision in neuroendocrine tumors (NETs) expected by April 3 this year. The FDA recently canceled an advisory committee meeting on that application, representing a positive sign for Exelixis, according to Citi analysts. Cabometyx has also posted some mixed data in metastatic castration-resistant prostate cancer. After the phase 3 CONTACT-02 trial missed its overall survival goal at the final analysis, Exelixis’ partner Ipsen called it quit on the indication in Europe.Exelixis itself previously appeared determined to pursue an U.S. approval. But, during the company’s fourth-quarter earnings call last week, CEO Michael Morrissey said the firm’s “singular focus right now from a regulatory point of view” is the NET indication and that it would circle back on prostate cancer once the expected NET approval is in the bag.Despite Cabometyx’s kidney cancer setback, Exelixis’ plan to grow beyond its bread and butter is taking shape. The company’s next-generation TKI, zanzalintinib, is approaching phase 3 readouts in colorectal cancer and non-clear cell renal cell carcinoma in the second half of 2025. In kidney cancer, Merck & Co. recently inked a collaboration with Exelixis to test zanzalintinib with the New Jersey pharma’s Welireg in two phase 3 studies.“We believe the collaboration with Merck provides a source of external validation to Exelixis’ strategic positioning of zanzalintinib as the next-generation version of Cabometyx,” William Blair analyst Andy Hsieh, Ph.D., said in a note when the deal was announced in October.As Hsieh noted, Merck already has the phase 3 LITESPARK-012 study evaluating the triplet of Welireg, Keytruda and Eisai-partnered Lenvima—as well as the co-formulated Keytruda and CTLA-4 inhibitor quavonlimab plus Lenvima—compared with the Keytruda-Lenvima doublet in first-line kidney cancer.“Given that Lenvima at the 20 mg dose had demonstrated tolerability challenges, we view Merck’s move to hedge its reliance on Lenvima as prudent,” Hsieh said.Exelixis has projected Cabometyx revenue will reach $3 billion in 2030 and that zanzalintinib could reach $5 billion in 2033 revenue. In 2024, the company generated $2.17 billion.

Phase 3Clinical ResultASCOImmunotherapy

22 Jan 2025

·www.prnewswire.com

Akeso Received Payment for the Development Collaboration on Tagitanlimab

HONG KONG, Jan. 22, 2025 /PRNewswire/ -- On January 22, 2025, Akeso Inc. (9926.HK) announced that it had received payment from Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. ("Sichuan Kelun") for their collaboration on the development of tagitanlimab, an innovative humanized monoclonal antibody targeting PD-L1, following its recent marketing approval by China's National Medical Products Administration. In 2014, Akeso signed a cooperation agreement with Sichuan Kelun for the development of tagitanlimab. Under the terms of the agreement, Akeso will receive royalties from the commercial sales of tagitanlimab in addition to the development payment. Tagitanlimab marks Akeso's second oncology product to yield commercial royalties, following pucotenlimab, a PD-1 monoclonal antibody developed in collaboration with Lepu Biopharma in 2016. Dr. Yu Xia, founder, chairwoman, president, and CEO of Akeso, said: "Congratulations to our partners. We are thrilled about continuously successful approval of our innovative products, and truly anticipate their outstanding commercialization performance. This achievement highlights Akeso's strong R&D capabilities and our commitment to innovation. Since its inception, Akeso has established multiple external collaborations, including ivonescimab with Summit Therapeutics, quavonlimab with Merck and pucotenlimab with Lepu Biopharma. These partnerships not only benefit patients but also deliver significant returns for both Akeso and our collaborators. Looking ahead, Akeso will continue to pursue a diversified strategy for new drug development, leveraging global resources to drive the high-quality commercialization of our independently developed innovative therapeutics." SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inDrug Approval

23 May 2024

·www.biopharmadive.com

ASCO24: An early look at cancer drug study results

BioPharma Dive is testing out a new format rounding up smaller updates from around the industry. Have thoughts on what could make this type of story better? Drop us a line!Today, were interrupting our usual rundown of industry news to highlight notable clinical trial updates ahead of next weeks American Society of Clinical Oncologys annual meeting. On Thursday, conference organizers released abstracts, or snapshots, of most of the studies set to be presented at the meeting, which will be held in Chicago from May 31 to June 4.Note: So-called late-breaking abstracts, which often feature particularly consequential trial findings, arent available until the day the relevant studies are presented. This year, that group includes anticipated data on Novartis therapy Scemblix in leukemia, GSKs Blenrep in multiple myeloma and AstraZeneca and Daiichi Sankyos Enhertu treatment in breast cancer.Abstract #9507: Analysts have closely tracked a dual-targeting antibody drug that Immunocore is developing for a type of skin cancer called cutaneous melanoma. Trial results included in an ASCO abstract showed that, among 31 evaluable people who previously received immunotherapy, Immunocores drug led to partial tumor responses in four, or 13%. Including study participants whose disease was considered stable, the so-called clinical benefit rate was 61%. Though slightly below analysts expectations, the data are roughly similar to the results for Bristol Myers Squibbs Odualag in a comparable patient population. Immuncore recently began a Phase 3 trial of its drug, called brenetafusp. Ned PagliaruloAbstracts #5502, 9506: Drugmakers have hoped that targeting an immune cell protein called TIGIT could build on the success seen with checkpoint inhibitors like Merck & Co.s Keytruda and Bristol Myers Squibbs Opdivo. But trial results to date have been mixed and new data included in ASCO abstracts Thursday probably wont settle any debates. On one hand, Phase 2 trial findings for Mercks TIGIT-targeting drug vibostolimab coformulated with Keytruda shrank or eliminated tumors in a larger share of women with a type of endometrial cancer than Keytruda alone. On the other, data from a Phase 1/2 trial of Keytruda, vibostolimab and a third experimental immunotherapy called quavonlimab in advanced melanoma patients werent good enough for the Merck to continue enrolling patients. Jonathan GardnerAbstract #3508: An experimental cocktail of six drugs substantially extended survival and delayed tumor growth, compared to a standard therapy, in people with previously treated metastatic colon cancer, according to an ASCO abstract. The regimen includes two drugs developed by Arcus Biosciences: etrumadenant, a so-called adenosine receptor antagonist, and zimberelimab, a checkpoint inhibitor. Median overall survival among the 75 patients randomized to the cocktail was 19.7 months, versus 9.5 months for the 37 given Stivarga in the Phase 1b/2 study. Arcus is closely partnered with Gilead Sciences, although their focus has been on developing zimberelimab and another immunotherapy. Ned PagliaruloAbstract #5010: Johnson & Johnson is one of many companies now exploring radiopharmaceuticals, which deliver radiation directly to a tumor. Its first chance to break into the field could be JNJ-6420, a drug that executives already billed as a potential future blockbuster. J&J aims to show the drug can slow tumor progression in men whose prostate cancer has progressed after hormone therapies. Early-stage study results disclosed in an abstract show the company may need to manage safety concerns. While 46% of men treated with a select drug dose had a 50% decrease in a marker associated with improved survival, 61% experienced an adverse event graded as severe or medically significant. Four of the 67 patients who received J&Js drug overall in the study died from adverse events. Jonathan GardnerAbstract #6502: Anyone looking for updated trial results on MorphoSys myelofibrosis drug pelabresib will have to wait for ASCO itself, as an abstract for the biotechnology companys MANIFEST-2 study only includes previously presented data. The drug is at the center of Novartis pending $2.9 billion acquisition of MorphoSys, but there are questions about its safety after a Stat report highlighted multiple cases of acute myeloid leukemia developing in pelabresib-treated patients. Ned Pagliarulo '

Clinical ResultASCOAcquisitionPhase 2Immunotherapy

100 Deals associated with Quavonlimab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Renal Cell Carcinoma	Phase 3	-	Akeso Biopharma Co., Ltd.	-
Non-small cell lung cancer stage IIIB	Phase 2	United States	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	China	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	Japan	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	Australia	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	Canada	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	Chile	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	France	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	Greece	Merck Sharp & Dohme Corp.	02 Jul 2017
Non-small cell lung cancer stage IIIB	Phase 2	Israel	Merck Sharp & Dohme Corp.	02 Jul 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03179436 (MK-1308-001 \| 1308-001, AACR2022) Manual	Phase 1/2	Locally Advanced Melanoma	151	quavonlimab+pembrolizumab	hsapovudkh(mkoqsbuixj) = arefmhylbs nrhtpqedth (xdhfgwsopw, 4.4 - 15.9) View more	Positive	15 Jun 2022
NCT03179436 (MK-1308-001 \| 1308-001, AACR2022) Manual	Phase 1/2	Locally Advanced Melanoma	151	quavonlimab	hsapovudkh(mkoqsbuixj) = fzhebotjoc nrhtpqedth (xdhfgwsopw, 0.1 - 13.2) View more	Positive	15 Jun 2022
NCT03179436 (MK-1308-001 \| 1308-001, Pubmed \| Lung Cancer) Manual	Phase 1/2	Extensive stage Small Cell Lung Cancer Second line	40	quavonlimab+pembrolizumab	smusreyilp(cbpophsizw) = tysagpqzds hyqnnheeug (tzqndqerzh ) View more	Positive	01 Sep 2021
NCT03179436 (MK-1308-001 \| 1308-001, ASCO2019)	Phase 1	Non-Small Cell Lung Cancer First line	213	MK-1308 plus pembrolizumab	kasktiehqk(zoxzbsitxe) = uqtbrqzkkf zktaniprms (hsfdbpvwbt ) View more	Positive	26 May 2019

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