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

February 11, 2025 updated by: GV20 Therapeutics

An Open-Label Phase 1/2A Study of GV20-0251 Monotherapy and GV20-0251 in Combination With Pembrolizumab in Participants With Advanced and/or Refractory Solid Tumor Malignancies

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1/2A non-randomized, open label, multi-center study to be conducted in four parts (Parts A, B, C and D).

In Part A, 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).

In Part B, 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 across multiple expansion cohorts involving eligible participants.

In Part C, 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 Part D, 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 across multiple expansion cohorts involving eligible participants.

Study Type

Interventional

Enrollment (Estimated)

365

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90025
        • Recruiting
        • The Angeles Clinic and Research Institute
        • Contact:
        • Principal Investigator:
          • Kristopher Wentzel, MD
    • Colorado
      • Denver, Colorado, United States, 80218
        • Not yet recruiting
        • HealthONE Clinic Services Oncology - Hematology, LLC d/b/a Sarah Cannon Research Institute at HealthONE
        • Principal Investigator:
          • Jason Henry, MD
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Patricia LoRusso, DO
    • Florida
      • Fort Myers, Florida, United States, 33916
        • Not yet recruiting
        • Florida Cancer Specialists & Research Institute, LLC
        • Contact:
        • Principal Investigator:
          • Judy Wang, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46256
        • Recruiting
        • Community Health Network, Inc.
        • Principal Investigator:
          • Bert O'Neil, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Justin Gainor, MD
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
        • Contact:
        • Principal Investigator:
          • M. Najeeb Al Hallak, MD
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health
        • Contact:
        • Principal Investigator:
          • Janice Mehnert, MD
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University
        • Principal Investigator:
          • Shivaani Kummar, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Not yet recruiting
        • Verdi Oncology Tennessee, Scri Oncology Partners
        • Principal Investigator:
          • Meredith Pelster, MD
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Oncology Consultants, P.A.
        • Contact:
        • Principal Investigator:
          • Jose Peguero, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas M. D. Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Aung Naing, MD
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Contact:
        • Principal Investigator:
          • Alexander Spira, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
    • Cutaneous melanoma
    • Non-small cell lung cancer
    • Proficient MMR (pMMR)/MSS adenocarcinoma of the colon or rectum (Parts C and D only)

Parts A, B, C and D Exclusion Criteria:

  • 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
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years from C1D1
  • Has received radiation therapy to the lung that is higher than 30 Gy within 6 months prior to C1D1 for NSCLC (Parts C and D only)
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years from C1D1 (Parts C and D only)
  • Has severe hypersensitivity ( ≥ Grade 3) to Pembrolizumab and/or any of its excipients (Parts C and D only)
  • Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease (Parts C and D only)
  • Has a condition, therapy, laboratory abnormality, or circumstance that could confound study results or interfere with full participation, making it unsuitable for the participant, as determined by the treating Investigator (Parts C and D only)
  • Active substance abuse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A - Dose Escalation in up to 7 dose levels
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
Increasing doses of GV20-0251 administered by intravenous (IV) infusion once or twice every 3 weeks as monotherapy.
Biological: GV20-0251
GV20-0251 preliminary RP2D administered by IV infusion as monotherapy.
Experimental: Part B - Multiple Expansion Cohorts in up to 4 tumor indications
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
Increasing doses of GV20-0251 administered by intravenous (IV) infusion once or twice every 3 weeks as monotherapy.
Biological: GV20-0251
GV20-0251 preliminary RP2D administered by IV infusion as monotherapy.
Experimental: Part C - GV20-0251 in Combination with Pembrolizumab Dose Escalation in 2-4 dose levels
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®]
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.
Other Names:
  • MK-3475
Biological: GV20-0251 and Pembrolizumab [KEYTRUDA®]
GV20-0251 administered by IV infusion at preliminary RP2D from Part C. 200 mg pembrolizumab administered by IV infusion once every 3 weeks.
Other Names:
  • MK-3475
Experimental: Part D - GV20-0251 in Combination with Pembrolizumab Dose Expansion in up to 5 indications
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®]
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.
Other Names:
  • MK-3475
Biological: GV20-0251 and Pembrolizumab [KEYTRUDA®]
GV20-0251 administered by IV infusion at preliminary RP2D from Part C. 200 mg pembrolizumab administered by IV infusion once every 3 weeks.
Other Names:
  • MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate ORR per RECIST version 1.1 (Parts B and D)
Time Frame: 12 months
ORR
12 months
Percentage of Participants With Adverse Events (Parts A and C)
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (Parts B and D)
Time Frame: 24 months
OS
24 months
Additional safety and tolerability
Time Frame: 24 months
TEAEs per NCI CTCAE version 5.0
24 months
Cmax of GV20-0251
Time Frame: 12 months
Maximum concentration
12 months
Tmax of GV20-0251
Time Frame: 12 months
Time to peak drug concentration
12 months
T1/2
Time Frame: 12 months
Terminal half-life of GV20-0251
12 months
AUC
Time Frame: 12 months
Area under the curve
12 months
ADAs
Time Frame: 12 months
Specification and quantification of anti-drug antibodies
12 months
nADAs
Time Frame: 12 months
Neutralizing anti-drug antibodies
12 months
DCR
Time Frame: 24 months
Disease Control Rate is the percentage of participants with stable disease, complete response or partial response among all response evaluable participants
24 months
DoR
Time Frame: 24 months
Duration of Response is the time from first CR/PR to the date of PD or death.
24 months
PFS
Time Frame: 24 months
Progression Free Survival is the duration from the first dose to PD/death
24 months
ORR (Parts A and C)
Time Frame: 24 months
Percentage of participants with complete response or partial response among all response evaluable participants
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To preliminarily evaluate the application of biomarkers to measures of efficacy and safety.
Time Frame: 12 months
Serial Measurement of Target Saturation after administration of GV20-0251.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GV20 Therapeutics

Collaborators

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2023

Primary Completion (Estimated)

December 15, 2026

Study Completion (Estimated)

September 5, 2027

Study Registration Dates

First Submitted

December 12, 2022

First Submitted That Met QC Criteria

December 21, 2022

First Posted (Actual)

December 30, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 11, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GV20-0251-100 (Other Identifier: GV20 Therapeutics)
  • MK-3475-F77 (Other Identifier: Merck)
  • KEYNOTE-F77 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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