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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- GV20 Therapeutics
- Enrollment
- 268
- Locations
- 13
- Primary Endpoint
- Objective Response Rate ORR per RECIST version 1.1 (Parts B and D)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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).
Intervention: GV20-0251 (Biological)
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.
Intervention: GV20-0251 (Biological)
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.
Intervention: GV20-0251 and Pembrolizumab [KEYTRUDA®] (Biological)
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.
Intervention: GV20-0251 and Pembrolizumab [KEYTRUDA®] (Biological)
Outcomes
Primary Outcomes
Objective Response Rate ORR per RECIST version 1.1 (Parts B and D)
Time Frame: 12 months
ORR
Percentage of Participants With Adverse Events (Parts A and C)
Time Frame: 12 months
Secondary Outcomes
- nADAs(12 months)
- 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)
- AUC(12 months)
- ADAs(12 months)
- DCR(24 months)
- DoR(24 months)
- PFS(24 months)
- ORR (Parts A and C)(24 months)