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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06295809




Registration number
NCT06295809
Ethics application status
Date submitted
29/02/2024
Date registered
6/03/2024
Date last updated
27/06/2024

Titles & IDs
Public title
A Study of (Neo)Adjuvant V940 and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007)
Scientific title
A Phase 2/3, Adaptive, Randomized, Open-label, Clinical Study to Evaluate Neoadjuvant and Adjuvant V940 (mRNA-4157) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care, and Pembrolizumab Monotherapy in Participants With Resectable Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (INTerpath-007)
Secondary ID [1] 0 0
2023-505712-37
Secondary ID [2] 0 0
V940-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Squamous Cell 0 0
Skin Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - V940
Treatment: Surgery - Surgery

Experimental: Pembrolizumab plus V940 with SOC - Participants will receive V940 1 mg intramuscular (IM) injection every 3 weeks (q3w) for up to 6 weeks and pembrolizumab 400 mg intravenous (IV) infusion every 6 weeks (q6w) up to 12 weeks as neoadjuvant therapy prior to surgery; followed by V940 1 mg IM injection q3w up to 21 weeks and pembrolizumab 400 mg IV infusion q6w or until discontinuation.

Active comparator: Standard of Care (SOC) - Participants will receive surgical resection as per local guidelines with/without adjuvant radiation therapy (RT) at investigator's discretion.

Experimental: Pembrolizumab with SOC - Participants will receive pembrolizumab 400 mg IV infusion q6w up to 12 weeks as neoadjuvant therapy prior to surgery; followed by pembrolizumab 400 mg IV infusion q6w or until discontinuation.


Treatment: Other: Pembrolizumab
IV Infusion

Treatment: Other: V940
IM injection

Treatment: Surgery: Surgery
Local resection of cancerous lesions of the skin
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival (EFS)
Timepoint [1] 0 0
Up to ~59 months
Secondary outcome [1] 0 0
Overall response rate (ORR)
Timepoint [1] 0 0
Up to ~38 months
Secondary outcome [2] 0 0
Freedom from surgery (FFS) rate
Timepoint [2] 0 0
Up to ~38 months
Secondary outcome [3] 0 0
Pathological complete response (pCR) rate
Timepoint [3] 0 0
Up to ~38 months
Secondary outcome [4] 0 0
Major pathological response (mPR) rate
Timepoint [4] 0 0
Up to ~38 months
Secondary outcome [5] 0 0
Disease-free survival (DFS)
Timepoint [5] 0 0
Up to ~59 months
Secondary outcome [6] 0 0
Disease-specific survival (DSS)
Timepoint [6] 0 0
Up to ~59 months
Secondary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
Up to ~59 months
Secondary outcome [8] 0 0
Percentage of participants who experience and adverse event (AE)
Timepoint [8] 0 0
Up to ~59 months
Secondary outcome [9] 0 0
Percentage of participants who discontinue study intervention due to AEs
Timepoint [9] 0 0
Up to ~19 months
Secondary outcome [10] 0 0
Change from baseline in Global health status/QoL score (QLQ-C30 Items 29 and 30)
Timepoint [10] 0 0
Baseline and up to ~38 months
Secondary outcome [11] 0 0
Change from baseline in physical functioning score of QLQ (C30 Items 1-5)
Timepoint [11] 0 0
Baseline and up to ~38 months
Secondary outcome [12] 0 0
Change from baseline in Role functioning score of QLQ-C30 Items 6-7
Timepoint [12] 0 0
Baseline and up to ~38 months

Eligibility
Key inclusion criteria
* 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 V940: 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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 V940 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
* Has a 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
* Has a history of allogeneic tissue/solid organ transplant
* Has not adequately recovered from major surgery or have ongoing surgical complications

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/05/2033
Actual
Sample size
Target
1012
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Gallipoli Medical Research Ltd-GMRF CTU ( Site 3206) - Greenslopes
Recruitment hospital [2] 0 0
One Clinical Research ( Site 3211) - Nedlands
Recruitment postcode(s) [1] 0 0
4120 - Greenslopes
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Chile
State/province [1] 0 0
Araucania
Country [2] 0 0
Chile
State/province [2] 0 0
Region M. De Santiago
Country [3] 0 0
France
State/province [3] 0 0
Paris
Country [4] 0 0
Israel
State/province [4] 0 0
Jerusalem
Country [5] 0 0
Israel
State/province [5] 0 0
Petah Tikva
Country [6] 0 0
Israel
State/province [6] 0 0
Ramat Gan
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
Norway
State/province [8] 0 0
Oslo
Country [9] 0 0
Spain
State/province [9] 0 0
Galicia
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid, Comunidad De
Country [11] 0 0
Spain
State/province [11] 0 0
Valenciana, Comunitat
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Moderna TX
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a two-part (Phase 2/Phase 3) study of V940, an individualized neoantigen therapy (INT), plus pembrolizumab in participants with locally resectable advanced cutaneous squamous cell carcinoma (LA cSCC). Phase 2 has three arms V940 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 V940 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 V940 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 V940 plus pembrolizumab with SOC and SOC only, without changing the inclusion/exclusion criteria for the additional enrollment or study endpoints.
Trial website
https://clinicaltrials.gov/study/NCT06295809
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06295809