vibostolimab (MK-7684) / Merck (MSD) - LARVOL DELTA

KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2039 ➔ Feb 2032 | Trial primary completion date: Feb 2039 ➔ Feb 2032

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial. (PubMed, Nat Med) - P1/2 | "Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 ."

IO biomarker • Journal • P1/2 data • Tumor mutational burden • Melanoma • Oncology • Solid Tumor • TIGIT • TMB

Association of biomarkers with response to vibostolimab coformulated with pembrolizumab in 2 cohorts of the phase 2 KEYVIBE-005 study (SITC 2024) - P2 | "Background In the multicohort phase 2 KEYVIBE-005 study (NCT05007106), the antitumor activity of vibostolimab (anti-T-cell immunoreceptor with Ig and ITIM domains [TIGIT]) coformulated with pembrolizumab (anti–PD-1; vibostolimab/pembrolizumab) was demonstrated in patients with previously treated advanced mismatch repair–deficient (dMMR) endometrial cancer (cohort B1; n = 40; ORR, 64%) and in patients with previously untreated advanced esophageal cancer treated with vibostolimab/pembrolizumab plus 5-fluorouracil and cisplatin (cohort E; n = 40; ORR, 53%). Ethics Approval The study protocol and all amendments were approved by the institutional review board or ethics committee at each institution. Consent All patients provided written informed consent."

Biomarker • IO biomarker • P2 data • Endometrial Cancer • Esophageal Cancer • Oncology • Solid Tumor • PD-L1 • PVR • TIGIT

KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KEYMAKER 02B: A randomized trial of pembrolizumab (pembro) alone or with investigational agents as first-line treatment for advanced melanoma (ESMO 2024) - P1/2 | "We present results from patients (pts) treated with pembro + vibostolimab (vibo; anti-TIGIT; arm 1), pembro alone (arm 2), quavonlimab (qmab; anti–CTLA-4) coformulated with pembro (qmab/pembro; arm 3), and qmab/pembro + lenvatinib (len; multitargeted TKI; arm 4). Pts were aged ≥18 y with previously untreated unresectable stage III or IV cutaneous melanoma who had measurable disease per RECIST v1.1 and an ECOG PS of 0 or 1, but no active brain metastases. Preliminary results from KEYMAKER-U02B showed promising antitumor activity for first-line pembro + vibo and qmab/pembro. Safety was generally manageable. Additional treatment arms will be reported when available."

Clinical • Metastases • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • TIGIT

Safety and efficacy of vibostolimab (anti-TIGIT) coformulated with pembrolizumab (vibo/pembro) in previously untreated advanced head and neck squamous cell carcinoma (HNSCC): Results from the phase II KEYVIBE-005 study (ESMO 2024) - P2 | "Background: In KEYNOTE-048, patients (pts) with recurrent or metastatic HNSCC and known PD-L1 status had a statistically significant improvement in OS with pembro monotherapy vs cetuximab + chemotherapy (known as the EXTREME regimen) in the PD-L1 combined positive score (CPS) ≥1 population (median, 12.3 vs 10.4 months; HR, 0.74; 95% CI, 0.61-0.89; P = 0.00080); a favorable safety profile was observed with pembro monotherapy. Antitumor activity was observed with vibo/pembro in pts with HNSCC with PD-L1 CPS ≥1; no new safety signals were observed."

Clinical • Metastases • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1 • TIGIT

KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma (ESMO 2024) - P1/2 | "We present initial results from arm 4 (pembro + MK-4830 [anti-ILT4]) and arm 5 (favezelimab [anti-LAG-3] coformulated with pembro [fave/pembro]) and updated results from arm 1 (pembro + vibostolimab [vibo; anti-TIGIT]), arm 2 (pembro + gebasaxturev [geba; coxsackievirus A21]), and arm 3 (pembro alone). Adults with resectable stage IIIB-D melanoma were randomly assigned to open arms. All arms had manageable safety in stage IIIB-D melanoma. With the promising antitumor activity observed in this study, further investigation of pembro + vibo and fave/pembro in this setting is warranted. RFS by major pathologic response will be presented."

Clinical • Melanoma • Oncology • Solid Tumor • TIGIT

KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2 ➔ P1/2

Metastases • Phase classification • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Vibostolimab Coformulated With Pembrolizumab vs Pembro Alone as Adjuvant Therapy for High-Risk Melanoma: Results of the Phase 3 KEYVIBE-010 Study (SMR 2024) - No abstract available

Clinical • P3 data • Melanoma • Oncology • Solid Tumor

Association of biomarkers with response to first-line (1L) vibostolimab (anti-TIGIT) coformulated with pembrolizumab (vibo/pembro) in advanced head and neck squamous cell carcinoma (HNSCC): Results from KEYVIBE-005 (ESMO 2024) - P2 | "In pts with PD-L1–positive HNSCC, PD-L1 and TMB showed trends of a positive association with response to 1L vibo/pembro; TIGIT, TcellinfGEP, and PVR did not show an association with response. Trends towards lower baseline ctDNA burden and larger on-treatment ctDNA decreases were observed in responders vs nonresponders, suggesting the utility of liquid biopsy for disease monitoring."

Biomarker • Clinical • IO biomarker • Metastases • Tumor mutational burden • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1 • TIGIT

Severe lichenoid drug eruption after pembrolizumab plus vibostolimab treatment in a patient with endometrial cancer (EADV 2024) - "Pembrolizumab plus vibostolimab therapy is an immunotherapy combination with clinical trials in the treatment of solid tumors. Although there is no case of lichenoid drug eruption related to this combination therapy in the literature, cutaneous side effects such as lichenoid drug eruption related to pembrolizumab use are frequently reported. The immunological mechanism of pembrolizumab-induced lichenoid drug reactions is thought to be a T cell-mediated response."

Clinical • IO biomarker • Dermatopathology • Endometrial Cancer • Lichen Planus • Oncology • Pruritus • Solid Tumor • NECTIN2 • PVR

The KEYVIBE program: vibostolimab and pembrolizumab for the treatment of advanced malignancies. (PubMed, Future Oncol) - "These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease."

Journal • Metastases • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • TIGIT

Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001) ( KEYVIBE-001) (clinicaltrials.gov) - P1 | N=470 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Vibostolimab coformulated with pembrolizumab (vibo/pembro) + chemotherapy (chemo) as first-line treatment for advanced esophageal cancer (ec): Results from cohort E of the phase II KEYVIBE-005 study (ESMO-GI 2024) - P2 | "Vibo/pembro + 5-FU + cisplatin had promising antitumor activity and manageable safety in pts with previously untreated advanced EC."

Clinical • IO biomarker • Metastases • P2 data • Dental Disorders • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Pneumonia • Squamous Cell Carcinoma • Stomatitis • TIGIT

Vibostolimab coformulated with pembrolizumab (vibo/pembro) for previously treated advanced mismatch repair–deficient (dMMR) endometrial cancer: Results from cohort B1 of the phase 2 KEYVIBE-005 study. (ASCO 2024) - P2 | "Vibo/pembro demonstrated durable antitumor activity and a manageable safety profile in pts with previously treated advanced dMMR endometrial cancer."

Metastases • Mismatch repair • P2 data • Endometrial Cancer • Immunology • Microsatellite Instability • Oncology • Rheumatology • Solid Tumor • MSI • TIGIT

Triplet combination treatments with pembrolizumab (pembro) for anti–PD-(L)1–refractory advanced melanoma: Preliminary results of the phase 1/2 KEYMAKER-U02A study. (ASCO 2024) - P1/2 | "We report results from arm 1 (pembro + quavonlimab [qmab] (anti-CTLA4) + vibostolimab [vibo] (anti-TIGIT)), arm 2 [pembro + qmab + lenvatinib [len] (TKI)), and arm 3 (pembro + ATRA [all-trans retinoic acid]) of KEYMAKER-U02A. Although objective responses were observed in some pts with anti–PD-(L)1–refractory melanoma, protocol-prespecified criteria for enrollment expansion were not met in any arm. The safety profile was manageable. Additional arms will be reported for this pt population with a high unmet need."

Metastases • P1/2 data • Melanoma • Nephrology • Oncology • Solid Tumor • TIGIT

Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001) ( KEYVIBE-001) (clinicaltrials.gov) - P1 | N=492 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2024 ➔ Aug 2024 | Trial primary completion date: Oct 2024 ➔ Aug 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Phase 2 KEYNOTE-057 cohort C: Coformulations of pembrolizumab (pembro) and favezelimab or vibostolimab for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC) (EAU 2024) - No abstract available

Clinical • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2032 ➔ Feb 2039 | Trial primary completion date: Feb 2032 ➔ Feb 2039

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pembrolizumab with favezelimab or vibostolimab for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Phase 2 KEYNOTE-057 cohort C. (ASCO-GU 2024) - P2 | "Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT02625961."

Clinical • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • LAG3 • TIGIT

KEYMAKER-U02 Substudy 02A: Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Melanoma • Oncology • Solid Tumor

KEYMAKER-U02 Substudy 02C: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Melanoma • Oncology • Solid Tumor

KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT. (PubMed, Front Immunol) - "In addition, we designed a single-chain variable fragment derived from the clinically tested monoclonal antibody Vibostolimab targeting TIGIT, and assessed its performance alongside the nanobodies...The excellent affinity, high specificity and rapid on-target uptake in mice bearing TIGIT- overexpressing tumors showed the promising diagnostic potential of nanobodies to noninvasively image high TIGIT expression within the tumor. These findings hold promise for clinical translation to aid patient selection and improve therapy response."

IO biomarker • Journal • Oncology • TIGIT

Incremental Gains Toward Better Outcomes in Small Cell Lung Cancer (THE ASCO POST) - "'The benefit was modest, and in my opinion, additional studies are warranted in better understanding biomarker testing in SCLC, including SLFN11,' said Dr. Leal. Further analysis of the biomarker data may reveal signals for differential benefits, according to Dr. Leal. 'I think this study highlighted that we can start selecting patients based on biomarkers-realizing that small cell lung cancer is not a 'one-size-fits-all' kind of disease and that we need to strategize treatment in a more rational way,' she added."

Biomarker • Media quote