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

KEYMAKER-U01 substudy 01A: Investigational agents + pembrolizumab (pembro) and chemotherapy (chemo) in untreated stage IV non-small cell lung cancer (NSCLC) (ESMO 2025) - P1/2 | "Methods Adults with untreated confirmed stage IV NSCLC, measurable disease per RECIST v1.1, and no EGFR , ALK , or ROS1 mutations received pembro 200 mg + chemo (carboplatin + paclitaxel [squamous] or pemetrexed [nonsquamous]) Q3W with vibostolimab IV 200 mg Q3W, boserolimab IV 30 mg Q6W, MK-4830 IV 800 mg Q3W, or MK-0482 IV 750 mg Q3W for 4 cycles, followed by pembro with the same investigational agent (+ pemetrexed for nonsquamous) for 35 total cycles or until PD or unacceptable toxicity. a Investigator-assessed per RECIST v1.1. Conclusions Pembro and chemo + investigational agents demonstrated antitumor activity similar to previous reports for pembro and chemo and manageable AEs in untreated stage IV squamous or nonsquamous NSCLC."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD27 • EGFR • ROS1 • TIGIT

KEYMAKER-U01 substudy 01A: Phase 1/2 study of pembrolizumab plus ifinatamab deruxtecan (I-DXd) or patritumab deruxtecan (HER3-DXd) with or without chemotherapy in untreated stage IV non–small-cell lung cancer. (ASCO 2025) - P1/2 | "KEYMAKER-U01 substudy 01A (NCT04165070) is a phase 1/2, two-part, rolling arm, open-label study assessing the efficacy and safety of pembrolizumab plus an investigational agent (part A: vibostolimab, boserolimab, MK-4830, and MK-0482; part B: I-DXd and HER3-DXd), with or without chemotherapy in untreated stage IV NSCLC...In Arms 5 and 6, participants will receive I-DXd plus pembrolizumab 200 mg Q3W (Arm 5) or I-DXd plus pembrolizumab with 4 cycles of carboplatin area under the curve 5 or 6 mg/ml/min (Arm 6); I-DXd dose will be at 8mg/kg...The primary endpoint is incidence of dose-limiting toxicities until the start of cycle 2, and AEs and treatment discontinuations due to AEs until 40 days after last treatment (90 days for serious AEs); secondary endpoints include ORR and DOR, both per RECIST v1.1 by BICR, and pharmacokinetic parameters, including maximum concentration (Cmax) and maximum trough concentration (Ctrough) of I-DXd and HER3-DXd. Enrollment will be..."

IO biomarker • Metastases • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ERBB3 • HER-2 • ROS1

KEYMAKER-U04 substudy 04B: First-line (1L) enfortumab vedotin (EV) plus pembrolizumab (pembro)-based immune checkpoint inhibitor (ICI) combinations for advanced urothelial cancer (UC). (ASCO-GU 2026) - P1/2 | " Adult pts without prior systemic therapy for la/mUC and an ECOG PS of 0-1 were randomized 1:1:1 to EV + coformulated favezelimab (fave; anti–LAG3)/pembro 800 mg/200 mg (arm A), EV + coformulated vibostolimab (vibo; anti-TIGIT)/pembro 200 mg/200 mg (arm B), and EV + pembro 200 mg (arm C). In pts with la/mUC, the addition of LAG3- or TIGIT-targeted ICIs to EV + pembro did not have a clinically significant impact on efficacy. No new safety signals were identified. Incidence of certain immune-mediated AEs was higher with pembro-containing coformulations compared to EV + pembro."

Checkpoint inhibition • Clinical • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • TIGIT

Novel pembrolizumab-based treatments as first-line therapy in advanced clear cell renal cell carcinoma: Substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial. (PubMed, Ann Oncol) - P1/2 | "Observed efficacy and safety of pembro plus lenva were confirmatory of prior observations for this combination. ORR was similar to reference for pembro plus lenva plus bel and qmab/pembro plus lenva, but not the other investigative arms. Further investigation of pembro plus lenva plus bel and qmab/pembro plus lenva versus pembro plus lenva is ongoing in the phase 3 LITESPARK-012 study."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

First-line pembrolizumab-based regimens for advanced clear cell renal cell carcinoma: KEYMAKER-U03 substudy 03A (ESMO 2025) - P1/2 | "Methods Adults with advanced ccRCC and no prior systemic therapy were randomized 2:1 to open investigational arms or the reference (ref): coformulated quavonlimab (qmab; anti-CTLA-4)/pembro + lenvatinib (lenva; VEGFR-TKI); coformulated favezelimab (fave; anti-LAG-3)/pembro + lenva; pembro + lenva + belzutifan (bel; HIF-2α inhibitor); coformulated vibostolimab (vibo; anti-TIGIT)/pembro + bel; ref, pembro + lenva. Other regimens did not show improved ORR and PFS compared with pembrolizumab + lenvatinib, yet the duration of follow-up was insufficient to detect long-term contributions to OS. Safety profiles were consistent with the profiles of the individual drugs in each regimen."

Clinical • Late-breaking abstract • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • EPAS1 • TIGIT

Phase 2 KEYNOTE-057 cohort C: Pembrolizumab (pembro) with vibostolimab or favezelimab for patients (pts) with high-risk (HR) bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). (ASCO-GU 2023) - P2 | "Efficacy will be evaluated in all pts who received ≥1 dose of study treatment and have a baseline evaluation consisting of pre-enrollment cystoscopy, TURBT/biopsy, urine cytology, and baseline CT urography imaging. Clinical trial information: NCT02625961."

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

KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma (AACR 2023) - P1/2 | "Neoadjuvant pembro + vibo, pembro + geba, and pembro alone followed by adjuvant pembro had manageable safety and promising antitumor activity in patients with stage IIIB-D melanoma. Of the combination treatments, pembro + vibo showed the most promise."

Clinical • Melanoma • Oncology • Solid Tumor • 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

A multicohort, open-label, phase 2 basket study of the coformulation of vibostolimab with pembrolizumab, with or without other anticancer therapies, in select solid tumors (AACR 2022) - P2 | "Enrollment is ongoing. >"

Clinical • IO biomarker • P2 data • Pan tumor • Oncology • Solid Tumor • CD4 • CD8 • 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

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

KEYSTEP-008: Pembrolizumab (pembro)-based combinations for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). (ASCO-GI 2026) - P2 | " Adults with stage IV colorectal adenocarcinoma, locally confirmed MSI-H/dMMR status and ECOG PS 0 or 1 were randomized 1:1 (cohort A) to coformulated quavonlimab (anti–CTLA-4; Qmab)/pembro (25 mg/400 mg) IV Q6W or pembro 400 mg IV Q6W or 1:1:1:1:1 (cohort B) to Qmab/pembro (25 mg/400 mg) IV Q6W, MK-4830 (anti-ILT4) 800 mg + pembro 200 mg IV Q3W, coformulated favezelimab (anti−LAG-3; fave)/pembro (800 mg/200 mg) IV Q3W, coformulated vibostolimab (anti-TIGIT; vibo)/pembro (200 mg/200 mg) IV Q3W, or pembro 400 mg IV Q6W. Pembro-based combinations evaluated in this study showed numerically higher ORR vs pembro alone, but the absolute improvement was modest, especially in the 1L setting. Despite manageable safety, these results do not support further clinical development of these combinations in pts with MSI-H/dMMR mCRC. NR, not reached."

dMMR • Metastases • Mismatch repair • MSI-H • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI • TIGIT

Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB to IV melanoma in the phase 3 KEYVIBE-010 trial: results from participants enrolled in China (ESMO Asia 2025) - P3 | "In Chinese pts with resected stage IIB-IV melanoma, adjuvant vibo/pembro did not provide additional clinical benefit vs pembro alone, consistent with the global population. Pembro monotherapy remains a standard of care in this setting."

Clinical • P3 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • TIGIT

VIBOSTOLIMAB AND PEMBROLIZUMAB COFORMULATION COMBINED WITH LENVATINIB FOR MISMATCH REPAIR-PROFICIENT ADVANCED ENDOMETRIAL CANCER: RESULTS FROM COHORT B2 OF THE PHASE 2 KEYVIBE-005 STUDY (IGCS 2025) - P2 | "40 participants received ≥1 dose of treatment (80% received only 1-line prior therapy, any setting [68% prior (neo)adjuvant therapy]). Median follow-up was 41.5 (range, 40.0-45.6) months at data cutoff (August 5, 2025). ORR per investigator was 43% (95% CI, 27%-59%) (Table 1)."

Late-breaking abstract • Metastases • Mismatch repair • P2 data • pMMR • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • TIGIT

Biomarker analysis of coformulation of vibostolimab with pembrolizumab (vibo/pembro) with or without docetaxel for metastatic non–small-cell lung cancer (mNSCLC) after chemotherapy and immunotherapy (SITC 2025) - P2 | "Additional biomarker data will be presented.Conclusions These biomarker analyses showed that higher TIGIT IHC was associated with numerically longer PFS and OS in participants with mNSCLC previously treated with an anti-PD-(L)1 and platinum-based chemotherapy receiving vibo/pembro with docetaxel; this benefit was not observed with vibo/pembro alone.Trial Registration ClinicalTrials.gov identifier, NCT04725188Ethics Approval The study was conducted in accordance with principles of Good Clinical Practice and approved by the appropriate institutional review boards and regulatory agencies. All participants provided written informed consent before enrolling.Abstract 508 Table 1View inline•Open as popupPFS and OS HRa estimates for biomarker subgroups"

Biomarker • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1 • TIGIT

Characterizing the immune landscape in melanoma upon αPD-1 and αTIGIT mAbs (ESMO 2025) - P3 | "However, studies combining pembrolizumab (anti-PD-1, pembro) and vibostolimab ( anti-TIGIT, vibo) have not met their primary endpoints: the adjuvant trial (NCT05665595) was terminated early due to futility, while in the neoadjuvant setting, the efficacy of pembro + vibo combination was similar to pembro alone (Dummer et al. The decrease of TIGIT-expressing cells following treatment could suggest depletion of recently activated cells but further analyses are needed to fully elucidate the mechanism of action and its impact on melanoma outcomes to improve future treatment approaches. Legal entity responsible for the study The authors."

Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL10 • TIGIT • TNFA

First-line pembrolizumab alone or with investigational agents for advanced melanoma: Updated results from the phase I/II KEYMAKER-U02 substudy 02B (ESMO 2025) - P1/2 | "Background Prior analysis of KEYMAKER-U02 substudy 02B (NCT04305054) showed promising activity for first-line vibostolimab (vibo) + pembrolizumab (pembro) and coformulated quavonlimab (qmab)/pembro in advanced melanoma. Manageable safety was observed across the first 4 arms (vibo + pembro, pembro alone, qmab/pembro; qmab/pembro + lenvatinib [len]). Updated results are presented, including from 2 previously unreported arms: coformulated favezelimab (fave; anti–LAG-3)/pembro and fave/pembro + all-trans retinoic acid (ATRA)...Conclusions Safety was manageable across arms. Moderate antitumor activity was observed with fave/pembro (arm 5); no additional benefit was observed with combining ATRA with fave/pembro (arm 6)."

Clinical • Metastases • P1/2 data • 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=146 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | N=90 ➔ 146

Enrollment change • Trial completion • Melanoma • Oncology • Solid Tumor

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=100 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | N=200 ➔ 100 | Trial completion date: Apr 2030 ➔ Aug 2025 | Trial primary completion date: Apr 2030 ➔ Aug 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Pharmacological and structural characterization of vibostolimab, a novel anti-TIGIT blocking antibody for cancer immunotherapy. (PubMed, J Immunother Cancer) - "Vibostolimab is a novel anti-TIGIT antibody that completely blocks CD155 binding and induces T-cell activation. From experiments using a mouse tumor model and mouse surrogate anti-TIGIT antibody, we demonstrate direct evidence where it not only activates cytotoxic T cells but also induces the activation of antigen-presenting cells. The clinical relevance of vibostolimab, based on these mechanisms, in combination with pembrolizumab was recently tested in registrational trials."

IO biomarker • Journal • Oncology • IL2 • PVR • TIGIT

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 | Trial completion date: Apr 2030 ➔ Oct 2025 | Trial primary completion date: Apr 2030 ➔ Oct 2025

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Vibostolimab Coformulated with Pembrolizumab in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: KEYNOTE-365 Cohort G. (PubMed, Eur Urol Focus) - P1/2 | "We found that this combination had limited antitumor activity, with side effects as expected for the two drugs individually. The KEYNOTE-365 trial is registered on ClinicalTrials.gov as NCT02861573."

Journal • Cardiovascular • Castration-Resistant Prostate Cancer • Dermatology • Genito-urinary Cancer • Oncology • Prostate Cancer • Pruritus • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

KEYMAKER-U02 Substudy 02B: Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=315 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2030 ➔ Apr 2026 | Trial primary completion date: Apr 2030 ➔ Apr 2026

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

KEYMAKER-U02 Substudy 02B: Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=315 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Oncology • Solid Tumor

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