A Study of GV20-0251 Monotherapy and GV20-0251 in Combination With Pembrolizumab in Participants With Solid Tumor Malignancies

NCT05669430 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: GV20-0251-100MK-3475-F77KEYNOTE-F77
• Study Type: interventional
• Target: 365
• Locations: 1 country
• Sites: 13

Brief Summary

This is a Phase 1/2A study of GV20-0251 being developed for the treatment of participants with advanced solid tumors, who are refractory to approved therapies or other standard of care.

Conditions

Solid Tumor, Adult; Refractory Cancer; Endometrial Carcinoma (EC); Squamous Head and Neck Carcinoma; pMMR/MSS Adenocarcinoma of the Colon or Rectum; Cutaneous Melanoma; Non-Small Cell Lung Cancer

Keywords

GV20-0251

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate ORR per RECIST version 1.1 (Parts B and D)

  ORR

  12 months

• Percentage of Participants With Adverse Events (Parts A and C)

  12 months

Secondary Outcomes (12)

• Overall Survival (Parts B and D)

  24 months

• Additional safety and tolerability

  24 months

• Cmax of GV20-0251

  12 months

• Tmax of GV20-0251

  12 months

• T1/2

  12 months

Study Arms (4)

Part A - Dose Escalation in up to 7 dose levels

EXPERIMENTAL

A 3+3 dose escalation scheme will be used to evaluate the safety and tolerability of GV20-0251, and to establish the maximum tolerated dose (MTD) or the preliminary recommended Phase 2 dose (RP2D).

Biological: GV20-0251

Part B - Multiple Expansion Cohorts in up to 4 tumor indications

EXPERIMENTAL

The Bayesian optimal design for Phase II (BOP2) will be utilized to further characterize the anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 at the preliminary RP2D in up to 4 expansion cohorts involving eligible participants.

Biological: GV20-0251

Part C - GV20-0251 in Combination with Pembrolizumab Dose Escalation in 2-4 dose levels

EXPERIMENTAL

The Bayesian optimal interval (BOIN) design will be employed to evaluate the safety and tolerability of GV20-0251 in combination with pembrolizumab, and to determine the MTD or the preliminary RP2D of this combination in selected tumor indications.

Biological: GV20-0251 and Pembrolizumab [KEYTRUDA®]

Part D - GV20-0251 in Combination with Pembrolizumab Dose Expansion in up to 5 indications

EXPERIMENTAL

The BOP2 will be applied to further characterize the anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 in combination with pembrolizumab at the preliminary RP2D in up to 5 expansion cohorts involving eligible participants.

Biological: GV20-0251 and Pembrolizumab [KEYTRUDA®]

Interventions

GV20-0251 BIOLOGICAL

Increasing doses of GV20-0251 administered by intravenous (IV) infusion once or twice every 3 weeks as monotherapy.

Part A - Dose Escalation in up to 7 dose levels

GV20-0251 and Pembrolizumab [KEYTRUDA®] BIOLOGICAL

GV20-0251 administered by IV infusion at 10 mg/kg once every 3 weeks or at increasing doses up to the preliminary RP2D determined in Part A. 200 mg pembrolizumab administered by IV infusion once every 3 weeks.

Also known as: MK-3475

Part C - GV20-0251 in Combination with Pembrolizumab Dose Escalation in 2-4 dose levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants ≥18 years of age
• Previously treated, histologically-confirmed advanced solid malignancy with progressive disease requiring therapy
• Refractory or intolerant to standard therapy(ies)
• Must have received, be not eligible or decline standard of care therapy
• Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
• For participants who have received prior treatment with a checkpoint inhibitor there must be documented disease progression
• ECOG performance status of 0 or 1
• Life expectancy of ≥ 12 weeks in Parts A and C and ≥ 24 weeks in Parts B and D
• Participants must be willing to provide fresh tumor biopsy (core biopsy) both pre-treatment (Parts A, B, C and D) and on-treatment (Parts A and B), if clinically feasible
• Disease-free of active second/secondary or prior malignancies for ≥ 2 years
• Laboratory test results within the required parameters
• Women of child bearing potential (WOCBP) and men must agree to use adequate contraception
• Parts B, C and D may include the following tumor types:
• Endometrial carcinoma
• Squamous head and neck carcinoma

You may not qualify if:

• Participant with acute leukemia or CLL (Parts A and B only)
• Participant with heart disease or unstable arrhythmia
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
• Participant has active autoimmune disease or other medical conditions requiring chronic systemic steroid or immunosuppressive therapy
• History of major organ transplant
• History of a bone marrow transplant
• Symptomatic central nervous system (CNS) malignancy or metastasis
• Serious nonmalignant disease
• Pregnant or nursing women
• Treatment with PD-1 and equivalent immune modulators or major surgery prior to the first dose of study medication
• Participants who are currently receiving any other investigational agent or have received an investigational agent within 4 weeks prior to the first dose of study medication
• Treatment with any anticancer treatments with 2-weeks prior to the first dose of study medication
• Radiation for symptomatic lesions must have been completed prior to the first dose of study medication
• Participants with liver metastases unless approved by the Sponsor
• Any history of an immune related ≥ Grade 3 AE attributed to prior cancer immunotherapy

Sponsors & Collaborators

• GV20 Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (13)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

RECRUITING

HealthONE Clinic Services Oncology - Hematology, LLC d/b/a Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

NOT YET RECRUITING

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

Florida Cancer Specialists & Research Institute, LLC

Fort Myers, Florida, 33916, United States

NOT YET RECRUITING

Community Health Network, Inc.

Indianapolis, Indiana, 46256, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center

Detroit, Michigan, 48201, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Verdi Oncology Tennessee, Scri Oncology Partners

Nashville, Tennessee, 37203, United States

NOT YET RECRUITING

Oncology Consultants, P.A.

Houston, Texas, 77030, United States

RECRUITING

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (2)

• Li Y, Wu X, Sheng C, Liu H, Liu H, Tang Y, Liu C, Ding Q, Xie B, Xiao X, Zheng R, Yu Q, Guo Z, Ma J, Wang J, Gao J, Tian M, Wang W, Zhou J, Jiang L, Gu M, Shi S, Paull M, Yang G, Yang W, Landau S, Bao X, Hu X, Liu XS, Xiao T. IGSF8 is an innate immune checkpoint and cancer immunotherapy target. Cell. 2024 May 23;187(11):2703-2716.e23. doi: 10.1016/j.cell.2024.03.039. Epub 2024 Apr 23.

  PMID: 38657602 BACKGROUND

• Wentzel, K., Peguero, J., Kummar, S., Lorusso, P., Mehnert, J. M., Spira, A. I., Naing, A., Hamid, O., Mehmi, I., Benhadji, K., Alland, L., Hu, X., Xiao, H., Bao, X., Chen, J., Gong, Y., Liu, X. S. ESMO 2024

  RESULT

Related Links

• IGSF8 is an innate immune checkpoint and cancer immunotherapy target
• A phase I/II, open-label study of the novel checkpoint IGSF8 inhibitor GV20-0251 in patients with advanced solid tumors

MeSH Terms

Conditions

Neoplasms; Endometrial Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

GV20 Therapeutics

CONTACT

617-256-2846; clinicaltrials@gv20tx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 30, 2022
• Study Start: March 23, 2023
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): September 5, 2027
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)