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
Conditions
Keywords
GV20-0251
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.
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.
Interventions
BIOLOGICALGV20-0251
Increasing doses of GV20-0251 administered by intravenous (IV) infusion once or twice every 3 weeks as monotherapy.
BIOLOGICALGV20-0251 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.
Sponsors
Merck Sharp & Dohme LLC
GV20 Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall Survival (Parts B and D) | 24 months | OS |
| 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 |
| nADAs | 12 months | Neutralizing anti-drug antibodies |
| Additional safety and tolerability | 24 months | TEAEs per NCI CTCAE version 5.0 |
Countries
United States
Contacts
Primary ContactGV20 Therapeutics
Outcome results
None listed