A Study of (Neo)Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007)

Stopped early · Phase 2/Phase 3

Conditions studied: Carcinoma, Squamous Cell, Skin Neoplasms

In brief

This is a two-part (Phase 2/Phase 3) study of intismeran autogene, an individualized neoantigen therapy (INT), plus pembrolizumab in participants with locally resectable advanced cutaneous squamous cell carcinoma (LA cSCC). Phase 2 has three arms intismeran autogene plus pembrolizumab given as neoadjuvant and adjuvant treatment with standard of care (SOC), standard of care (surgical resection with/without adjuvant radiation therapy (RT) only at investigator's discretion) and pembrolizumab monotherapy given as neoadjuvant and adjuvant treatment with SOC. This phase will assess the safety and efficacy of intismeran autogene in combination with pembrolizumab as neoadjuvant and adjuvant therapy in participants with resectable LA cSCC as compared to standard of care SOC only. The primary hypothesis is that intismeran autogene plus pembrolizumab with SOC is superior to SOC only with respect to event free survival (EFS) as assessed by the investigator. Phase 3 expansion will be determined by prespecified Go-No-Go decision in which 412 additional participants will be randomized to intismeran autogene plus pembrolizumab with SOC and SOC only, without changing the inclusion/exclusion criteria for the additional enrollment or study endpoints. As of Amendment 04, enrollment was stopped and there will be no Phase 3 expansion.

Key facts

Study ID

NCT06295809

Run by

Merck Sharp & Dohme LLC

People needed

46

Starts

2024-04-18

Expected to finish

2026-03-05

Last updated by the study team

2026-05-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Has a histologically confirmed diagnosis of resectable cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted).
• Has LA Stage II-IV (M0) cSCC without distant metastases.
• cSCC must be amenable to surgery (resectable) with curative intent.
• Has a formalin-fixed, paraffin-embedded (FFPE) tumor sample available or is able to provide one that is suitable for the Next-generation Sequencing (NGS) required for this study.
• For males, agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving adjuvant radiation therapy (RT), and for ≥3 months after the last dose of study intervention
• Is female and not pregnant/breastfeeding and at least one of the following applies during the study : is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) at least during use of intismeran autogene: 15 days, Pembrolizumab: 120 days, Adjuvant RT, if performed: 90 days after last exposure or is a WOCBP who is abstinent from heterosexual intercourse.
• Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
• Has a life expectancy of >3 months per investigator assessment.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 14 days before randomization.
• Has adequate organ function.
• If hepatitis B surface antigen (HBsAg) positive, must have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
• If there is a history of hepatitis C virus (HCV) infection, HCV viral load must be undetectable at screening
• If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)

You may not qualify if…

• Has any other histologic type of skin cancer other than invasive cSCC as well as mixed histology, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, Merkel cell carcinoma (MCC), or melanoma
• Has distant metastatic disease (M1), visceral and/or distant nodal
• Has received prior therapy with an anti-programmed cell death receptor 1 (anti-PD-1), anti-programmed cell death receptor ligand 1 (anti-PD-L1), or anti-programmed cell death receptor ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte associated protein 4 (CTLA-4), OX-40, CD137)
• Has received prior systemic anticancer therapy including investigational agents for cSCC before randomization
• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the screening blood sample (including the NGS blood sample)
• Has received prior treatment with another cancer vaccine
• Has received prior radiotherapy to the index lesion (in-field lesion). Must have recovered from all radiation-related toxicities prior to randomization and not have had radiation pneumonitis
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
• History of chronic lymphocytic leukemia (CLL)
• History of central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to either intismeran autogene or pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
• Has had a myocardial infarction within 6 months of randomization
• History of allogeneic tissue/solid organ transplant
• Has not adequately recovered from major surgery or have ongoing surgical complications

Where it is running

• Hoag Memorial Hospital Presbyterian ( Site 1122) — Newport Beach, California, United States
• Stanford Cancer Center ( Site 1109) — Palo Alto, California, United States
• University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 1103) — Sacramento, California, United States
• Winship Cancer Institute, Emory University ( Site 1151) — Atlanta, Georgia, United States
• University of Iowa-Holden Comprehensive Cancer Center ( Site 1118) — Iowa City, Iowa, United States
• University of Kentucky Chandler Medical Center ( Site 1101) — Lexington, Kentucky, United States
• Ochsner Clinic Foundation ( Site 1113) — New Orleans, Louisiana, United States
• Massachusetts General Hospital ( Site 1162) — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute ( Site 1130) — Boston, Massachusetts, United States
• Washington University School of Medicine-Internal Medicine/Oncology ( Site 1100) — St Louis, Missouri, United States
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 1125) — Hackensack, New Jersey, United States
• Atlantic Health System Morristown Medical Center ( Site 1136) — Morristown, New Jersey, United States
• Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 1160) — Mineola, New York, United States
• Laura and Isaac Perlmutter Cancer Center ( Site 1121) — New York, New York, United States
• Providence Portland Medical Center ( Site 1102) — Portland, Oregon, United States
• UPMC Hillman Cancer Center ( Site 1107) — Pittsburgh, Pennsylvania, United States
• Avera Cancer Institute- Research ( Site 1161) — Sioux Falls, South Dakota, United States
• University of Virginia Health System ( Site 1115) — Charlottesville, Virginia, United States
• Inova Schar Cancer Institute ( Site 1108) — Fairfax, Virginia, United States
• University Hospital and UW Health Clinics ( Site 1119) — Madison, Wisconsin, United States
• Instituto de Investigaciones Clínicas Mar del Plata ( Site 1213) — Mar del Plata, Buenos Aires, Argentina
• Fundacion Estudios Clinicos-Oncology ( Site 1205) — Rosario, Santa Fe Province, Argentina
• Sanatorio Finochietto ( Site 1202) — Buenos Aires, Argentina
• Investigaciones Clinicas Moleculares (ICM) ( Site 1212) — CABA, Argentina
• USC/Norris Comprehensive Cancer Center ( Site 1112) — Los Angeles, California, United States

Full record on ClinicalTrials.gov

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