LIGHTBEAM-U01 Substudy 01B: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors

This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL), solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H), or advanced melanoma. This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment.
There will be no hypothesis testing in this study.

Start Date05 Jul 2024

Sponsor / Collaborator

Merck Sharp & Dohme LLC

EUCTR2021-004564-94-PL / Not yet recruitingPhase 3

A Randomized, Double-Blind, Phase 3 Study of Pembrolizumab/Vibostolimab Coformulation (MK-7684A) in Combination with Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants with Metastatic Non-Small Cell Lung Cancer (MK-7684A-007/KEYVIBE-007) - A Phase 3 study of MK-7684A in combination with chemotherapy in metastatic NSCLC

Start Date21 Feb 2022

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT04305054 / RecruitingPhase 1/2

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 02B

Substudy 02B 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 02B is to evaluate the safety and efficacy of investigational treatment arms in participants with 1L advanced melanoma and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/pembrolizumab monotherapy.
Arm 1: Pembrolizumab + Vibostolimab was added in the base protocol on 13-Nov-2019, and enrollment into this arm has been completed. Arm 2: Pembrolizumab was added in the base protocol on 13-Nov-2019, and enrollment stopped prematurely on 15-Aug-2022. Arm 3: Coformulation Pembrolizumab/Quavonlimab was added in Amendment 01 on 20-Oct-2020, and enrollment stopped prematurely on 15-Aug-2022. Arm 4: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib was added in Amendment 01 on 20-Oct-2020, and enrollment is ongoing. Arm 5: Coformulation Favezelimab/Pembrolizumab, Arm 6: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA), and Arm 7: Coformulation Favezelimab/Pembrolizumab + Vibostolimab were added in Amendment 04 on 10-May-2023, and enrollment for these arms will be initiated in July 2023.

Start Date01 Jul 2020

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Vibostolimab

100 Translational Medicine associated with Vibostolimab

100 Patents (Medical) associated with Vibostolimab

Literatures (Medical) associated with Vibostolimab

01 Aug 2023·Cancer letters

TIGIT immune checkpoint blockade enhances immunity of human peripheral blood NK cells against castration-resistant prostate cancer

Article

Author: Xing, Nianzeng ; Wang, Jing ; Li, Jianxing ; Ma, Jianlin ; Wang, Fangming ; Liu, Fei ; Yang, Feiya ; Liang, Jing ; Xu, Tianli ; Liu, Shuai ; Liu, Donghua

Castration-resistant prostate cancer (CRPC) patients have a 14-month median survival, emphasizing the need for alternative treatments. Previously, we demonstrated that expanded high-dose natural killer (NK) cells derived from human peripheral blood exhibit therapeutic efficacy against CRPC. However, which immune checkpoint blockade promotes NK cell antitumor immunity against CRPC remains unknown. Here, we explored immune checkpoint molecule expression in NK and CRPC cells during their interactions, and identified that the T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) monoclonal antibody (mAb), vibostolimab, significantly enhanced NK cell cytotoxicity against CRPC cells and cytokine production in vitro, demonstrated by upregulation of degranulation marker CD107a and Fas-ligand (Fas-L) and increased interferon-gamma (IFN-γ) and tumor necrosis factor-alpha secretion. TIGIT blockade increased Fas-L expression and IFN-γ production via the NF-κB signaling pathway and restored degranulation via the mitogen-activated protein kinase ERK (extracellular signal-regulated kinase) kinase/ERK pathway in activated NK cells. Vibostolimab significantly enhanced NK cell antitumor effects against CRPC in two xenograft mouse models. Vibostolimab also increased T cell chemotaxis induced by activated NK cells in vitro and in vivo. Overall, blocking TIGIT/CD155 signaling enhances the antitumor effect of expanded NK cells against CRPC; this finding supports the translational application of TIGIT mAb and NK cell combination strategies from bench to bedside for CRPC treatment.

01 Apr 2023·ESMO open

Anti-TIGIT therapies for solid tumors: a systematic review

Review

Author: Barlesi, F ; Rousseau, A ; Parisi, C

Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in cancer treatment, however not all patients benefit from it. Thus new therapies are under investigation, such as anti-TIGIT [anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains] antibodies. TIGIT is an immune checkpoint inhibiting lymphocyte T cells by several mechanisms. In vitro models showed its inhibition could restore antitumor response. Furthermore, its association with anti-PD-(L)1 therapies could synergistically improve survival. We carried out a review of the clinical trial about TIGIT referenced in the PubMed database, finding three published clinical trials on anti-TIGIT therapies. Vibostolimab was evaluated in a phase I alone or in combination with pembrolizumab. The combination had an objective response rate of 26% in patients with a non-small-cell lung cancer (NSCLC) naïve of anti-programmed cell death protein 1 (anti-PD-1). Etigilimab was tested in a phase I alone or in combination with nivolumab, but the study was stopped due to business reasons. In the phase II CITYSCAPE trial, tiragolumab demonstrated higher objective response rate and progression-free survival in combination with atezolizumab than atezolizumab alone in advanced PD-L1-high NSCLC. The ClinicalTrials.gov database references 70 trials of anti-TIGIT in patients with cancer, 47 of them with ongoing recruitment. Only seven were phase III, including five about patients with NSCLC, mostly with combination therapy. Data from phase I-II trials highlighted that targeting TIGIT represents a safe therapeutic approach, with an acceptable toxicity profile maintained when adding anti-PD-(L)1 antibodies. Frequent adverse events were pruritus, rash, and fatigue. Grade 3-4 adverse events were reported in nearly one in three patients. Anti-TIGIT antibodies are under development as a novel immunotherapy approach. A promising research area includes the combination with anti-PD-1 therapies in advanced NSCLCs.

01 Feb 2022·Annals of oncology : official journal of the European Society for Medical Oncology

Anti-TIGIT to overcome resistance to immune checkpoint inhibitors in lung cancer: limits and potentials

Communications

Author: de Marinis, F ; Passaro, A ; Attili, I

In the immune checkpoint era, the clin. course of advanced or metastatic non-small-cell lung cancer (NSCLC) has remarkably improved.Treatment with immune check-point inhibitors (ICIs), namely anti-programmed cell death protein 1 (PD-1) and anti-programmed death-ligand 1 (PD- L1), has led to impressive long-term survival outcomes in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type (wt) NSCLC, either as monotherapy (in the first-line setting for PD-L1 50% tumors) or in combination with platinum-based chemotherapy, in both squamous and non-squamous histol.Herein authors present the first-in-human phase I trial of vibostolimab, an anti-TIGIT humanized IgG1 (IgG1) monoclonal antibody, alone or in combination with pembrolizumab.Among the 76 patients in the dose-finding part A (15 with NSCLC), overall response rate (ORR) was 0% with vibostolimab monotherapy and 7% with the combination and in part B, 106 NSCLC patients were treated.As TIGIT coexists with other immune signals with regulatory functions and competitive binding on the same immune pathway, co-targeting more components of the pathway would be synergistic, as it was demonstrated in the preclin. setting.In addition, as TIGIT is expressed on different immune cells, the most appealing approach to tailor anti-TIGIT treatment would be to better define the TME compositionIndeed, the adoption of Fc-competent IgG1 anti-TIGIT compounds (e.g. tiragolumab, vibostolimab) potently activates antigen-presenting cells and enhances T-cell activation through pro-inflammatory cytokines and chemokines.Results clearly highlight that single-agent anti-TIGIT is not effective, whereas the coadministration with an anti-PD-1 or anti-PD-L1 is needed to exert immune antitumor activity.

News (Medical) associated with Vibostolimab

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

13 May 2024

·www.fiercebiotech.com

Merck halts phase 3 TIGIT trial after immune-mediated adverse events prompt discontinuations

Merck is continuing with four other phase 3 lung cancer trials involving vibostolimab. Merck & Co. has bailed early on a phase 3 test of the anti-TIGIT antibody vibostolimab after a high rate of discontinuations rendered the trial's success unlikely. The Big Pharma had been evaluating vibostolimab in combination with anti-PD-1 immunotherapy Keytruda in the KeyVibe-010 trial as an adjuvant treatment for patients with resected high-risk melanoma. But a higher rate of discontinuations mainly due to “immune-mediated adverse experiences” among patients taking the combination regimen meant it was “highly unlikely that the trial could achieve a statistically significant improvement” in the primary endpoint of recurrence-free survival, the company said. As a result, the independent data monitoring committee recommended that Merck unblind the trial and offer all patients the option of receiving just Keytruda. The study had originally been expected to read out in 2026. “Through our clinical development program, we continue to ask the tough questions in an effort to fully explore the potential of novel co-formulations and combinations that build on the foundation of Keytruda, with a goal to improve upon current standards of care and help even more patients with cancer,” Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, said in the May 13 release. This is not the first time vibostolimab has run into problems in the clinic. Last year, Merck revealed that a combination of vibostolimab and Keytruda was numerically less effective than the chemotherapy docetaxel in terms of progression-free survival among non-small cell lung cancer patients. It’s still not the end of the road for vibostolimab, however. Merck has four other phase 3 lung cancer trials involving the antibody ongoing with a combined total of about 3,000 patients enrolled. None of these trials are expected to be altered in the wake of today’s news, the company stressed. Talking to investors at an event back in December 2023, Merck’s chief medical officer Eliav Barr, M.D., identified phase 3 as where TIGITs would need to prove their worth. “We have to acknowledge that there have been phase 2 studies that have looked good, and then there's been phase 3s that have been more complex. So, the way I see the compound is we would wait to see phase 3 and go from there,” Barr said at the time. Merck’s executives can take some comfort from the fact that their Big Pharma peers have also struggled to demonstrate the effect of TIGIT blockade on cancer, despite the high hopes once heaped on the modality. Still, the year got off to a decent start with Roche posting a phase 3 win for tiragolumab in esophageal cancer, even if the use of a comparator that is no longer the standard of care complicates efforts to tease out the antibody's impact.

Phase 3Phase 2Immunotherapy

13 May 2024

·firstwordpharma.com

Adverse events scupper melanoma study of Merck & Co.'s TIGIT, Keytruda combo

ASCO Daily Digest – your go-to-source for the key developments emerging from this year's American Society of Clinical Oncology (ASCO) annual meeting. Exclusively for PLUS subscribers – sign up here! Merck & Co. will stop dosing a coformulation of its anti-TIGIT antibody vibostolimab with Keytruda (pembrolizumab) in a Phase III study of patients with high-risk melanoma due to a higher rate of discontinuations observed in that arm of the study.The KeyVibe-010 trial is evaluating the coformulation, dubbed MK-7684A, versus Keytruda alone as adjuvant treatment in 1594 patients with resected high-risk Stage IIB-IV melanoma. According to Merck, a pre-planned analysis indicated that the study was "highly unlikely" to show a treatment benefit on the primary endpoint of recurrence-free survival (RFS).Immune-mediated AEsCompared to Keytruda alone, Merck said there was a higher dropout rate in the coformulation arm, primarily due to immune-mediated adverse experiences. An independent data monitoring committee has recommended that Merck unblind the study and allow patients in the coformulation arm to receive Keytruda monotherapy."Through our clinical development programme, we continue to ask the tough questions," remarked Marjorie Green, head of oncology, global clinical development at Merck Research Laboratories. The company's other ongoing Phase III studies of vibostolimab coformulated with Keytruda in lung cancer include KeyVibe-003, KeyVibe-006, KeyVibe-007 and KeyVibe-008.Vibostolimab has faced clinical setbacks before. Last year, Merck disclosed that when combined with Keytruda, vibostolimab showed no benefit compared to standard care with docetaxel in terms of progression-free survival (PFS) in previously treated patients with non-small-cell lung cancer (NSCLC), nor did it show a significant benefit when the coformulation was added to docetaxel. Those findings were from the Phase II KeyVibe-002 trial.Bigger opportunity in lung cancerIn a note to clients Monday, Morgan Stanley called the setback "an incremental negative" for vibostolimab, "but acknowledge that the lung programme is ongoing, which represents the more significant market opportunity and we await release of the full data from [the drug] in melanoma."Despite some renewed hope around TIGIT inhibition, the target's track record has been underwhelming, marked by some high-profile fails, most notably Roche's Fc-intact anti-TIGIT antibody tiragolumab missing the mark in two critical lung cancer trials. But interim data from the Phase III SKYSCRAPER-01 study released last year showed promising overall survival in NSCLC patients given tiragolumab on top of Roche's PD-L1 drug Tecentriq (atezoluzumab).Meanwhile, the analysts at Morgan Stanley point out that "not every TIGIT antibody is the same," with Gilead Sciences and Arcus Biosciences’ domvanalimab potentially offering an improved toxicity profile due to its Fc-silent structure. The analysts note that, like tiragolumab, Merck's TIGIT also has an intact Fc domain. They estimate that vibostolimab could generate sales of $4.6 billion in 2033, which is about five years after key patents on Keytruda are set to expire.For more on how Merck is plotting its course after exclusivity on the immunotherapy runs out, see Spotlight On: Winrevair approval could help Merck & Co. overcome its Keytruda issues.

Phase 3Clinical ResultASCOPhase 2Immunotherapy

100 Deals associated with Vibostolimab

External Link

KEGG	Wiki	ATC	Drug Bank
D11795	-	-	DB16420

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 3	US	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	CN	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	CL	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	GT	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	RU	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	KR	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	TR	Merck Sharp & Dohme Corp.	07 Apr 2021
Non-Small Cell Lung Cancer	Phase 3	UA	Merck Sharp & Dohme Corp.	07 Apr 2021
Hematologic Neoplasms	Phase 2	-	Merck Sharp & Dohme LLC	05 Jul 2024
Solid tumor	Phase 2	-	Merck Sharp & Dohme LLC	05 Jul 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


TIGIT (NEWS) Manual	Phase 2	metastatic non-small cell lung cancer	-	vibostolimab+Keytruda	sobvpqfqin(bvbwwfsmts) = rdzcckfags hwvhkqlchr (beptjbomnj ) View more	Negative	07 Dec 2023
				docetaxel	sobvpqfqin(bvbwwfsmts) = ofjqehoklh hwvhkqlchr (beptjbomnj ) View more
NCT04303169 (KEYMAKER-U02 substudy 02C \| 3475-02C \| KEYMAKER-U02 \| MK-3475-02C, AACR2023) Manual	Phase 1/2	Melanoma Neoadjuvant	66	pembrolizumab+vibostolimab (arm 1)	ddeqzmvkpw(mlriimjfww) = hymxzepjwk eazuqkifys (nujlwmgtdi ) View more	Positive	14 Apr 2023
				pembrolizumab+gebasaxturev (arm 2)	ddeqzmvkpw(mlriimjfww) = vhuistrzeo eazuqkifys (nujlwmgtdi ) View more
NCT02964013 (KEYVIBE-001, ESMO_GI2022)	Phase 1	Advanced gastric carcinoma PD-L1-positive	27	Vibostolimab 200mg + Pembrolizumab 200mg	icqngmaaco(eryufugirp) = bdbneckrfy prixioenwc (mjdjnjmmsu ) View more	Positive	02 Jul 2022
NCT02964013 (MK-7684-001, AACR2022) Manual	Phase 1	Uterine Cervical Cancer Third line	80	vibostolimab 200 mg+pembrolizumab	kemzqhtelm(ychtxkdisi) = athaufdshj zxckulwqdc (xrykbwryxm ) View more	Positive	15 Jun 2022
				vibostolimab 700 mg+pembrolizumab	kemzqhtelm(ychtxkdisi) = jqsazwslhs zxckulwqdc (xrykbwryxm ) View more
NCT02964013 (MK-7684-001 \| KEYVIBE-001 \| 7684-001, AACR2022) Manual	Phase 1	Ovarian Cancer Second line PD-L1 Expression	61	vibostolimab+pembrolizumab	-	Positive	15 Jun 2022
				vibostolimab/pembrolizumab
NCT02964013 (Pubmed)	Phase 1	HR-positive/HER2-low Solid Tumors \| Non-Small Cell Lung Cancer	76	Vibostolimab	vcfoarzodh(hqexektttb) = vegfmwapai dnualaffel (walgmelsem ) View more	-	17 Nov 2021
				Pembrolizumab	kivkcolyvx(uwjzmhjvqr) = cjidhlkgsw rzxcrdfkik (tnkckkxmnc ) View more
NCT02964013 (MK-7684-001 \| KEYVIBE-001 \| 7684-001, ESMO2020) Manual	Phase 1	Non-Small Cell Lung Cancer	41	Pembrolizumab+vibostolimab	rhzelpfplq(onddwyttcr) = aqkgzpvlov ealbwmeufk (qjmytryebe ) View more	Positive	17 Sep 2020
NCT02964013 (MK-7684-001 \| KEYVIBE-001 \| 7684-001, ESMO2020) Manual	Phase 1	Non-Small Cell Lung Cancer	79	Vibostolimab	fqeesupdce(vmijcbsvpf) = vaycvlwbao gakpemdkmk (dkcyaizzuu ) View more	Positive	17 Sep 2020
				Vibostolimab+pembrolizumab	fqeesupdce(vmijcbsvpf) = vxtvfygyrs gakpemdkmk (dkcyaizzuu ) View more

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