A Study of GV20-0251 Monotherapy and GV20-0251 in Combination With Pembrolizumab in Participants With Solid Tumor Malignancies
- Conditions
- Solid Tumor, AdultRefractory CancerEndometrial Carcinoma (EC)Squamous Head and Neck CarcinomapMMR/MSS Adenocarcinoma of the Colon or RectumCutaneous MelanomaNon-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05669430
- Lead Sponsor
- GV20 Therapeutics
- Brief Summary
This is a Phase 1 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 268
-
Participants ≥18 years of age
-
Previously treated, histologically-confirmed advanced solid malignancy with progressive disease requiring therapy
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Refractory or intolerant to standard therapy(ies)
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Must have received, be not eligible or decline standard of care therapy
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Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
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For participants who have received prior treatment with a checkpoint inhibitor there must be documented disease progression
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ECOG performance status of 0 or 1
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Life expectancy of ≥ 12 weeks in Parts A and C and ≥ 24 weeks in Parts B and D
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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
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Disease-free of active second/secondary or prior malignancies for ≥ 2 years
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Laboratory test results within the required parameters
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Women of child bearing potential (WOCBP) and men must agree to use adequate contraception
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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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part C - GV20-0251 in Combination with Pembrolizumab Dose Escalation in 2-4 dose levels GV20-0251 and Pembrolizumab [KEYTRUDA®] 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. Part B - Multiple Expansion Cohorts in up to 4 tumor indications GV20-0251 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. Part D - GV20-0251 in Combination with Pembrolizumab Dose Expansion in up to 5 indications GV20-0251 and Pembrolizumab [KEYTRUDA®] 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. Part A - Dose Escalation in up to 7 dose levels GV20-0251 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).
- Primary Outcome Measures
Name Time Method Objective Response Rate ORR per RECIST version 1.1 (Parts B and D) 12 months ORR
Percentage of Participants With Adverse Events (Parts A and C) 12 months
- Secondary Outcome Measures
Name Time Method Overall Survival (Parts B and D) 24 months OS
Additional safety and tolerability 24 months TEAEs per NCI CTCAE version 5.0
Cmax of GV20-0251 12 months Maximum concentration
Tmax of GV20-0251 12 months Time to peak drug concentration
T1/2 12 months Terminal half-life of GV20-0251
AUC 12 months Area under the curve
ADAs 12 months Specification and quantification of anti-drug antibodies
nADAs 12 months Neutralizing anti-drug antibodies
DCR 24 months Disease Control Rate is the percentage of participants with stable disease, complete response or partial response among all response evaluable participants
DoR 24 months Duration of Response is the time from first CR/PR to the date of PD or death.
PFS 24 months Progression Free Survival is the duration from the first dose to PD/death
ORR (Parts A and C) 24 months Percentage of participants with complete response or partial response among all response evaluable participants
Trial Locations
- Locations (13)
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
HealthONE Clinic Services Oncology - Hematology, LLC d/b/a Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists & Research Institute, LLC
🇺🇸Fort Myers, Florida, United States
Community Health Network, Inc.
🇺🇸Indianapolis, Indiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
NYU Langone Health
🇺🇸New York, New York, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Verdi Oncology Tennessee, Scri Oncology Partners
🇺🇸Nashville, Tennessee, United States
Oncology Consultants, P.A.
🇺🇸Houston, Texas, United States
The University of Texas M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States