A Study of GV20-0251 in Patients With Solid Tumor Malignancies

Study Overview
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Brief Summary
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This is a Phase 1 study of GV20-0251 being developed for the treatment of patients with advanced solid tumors, who are refractory to approved therapies or other standard of care.

Detailed Description
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This is a Phase 1 non-randomized, open label, multi-center study to be conducted in two parts (Parts A and B). Part A involves a 3 + 3 dose escalation scheme to evaluate safety and dose limiting toxicities (DLTs) and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 (RP2D) of GV20-0251. Part B is a cohort expansion in which eligible patients will be treated at the RP2D of GV20-0251 to further characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of GV20-0251 as well as to evaluate anti-tumor activity in patients with selected malignancies. The study consists of a Screening Period, a Treatment Period, an End of Treatment Visit, Safety Follow-Up Period and a Survival Follow-Up Period.

Official Title
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An Open-Label Study of GV20-0251 in Patients With Advanced and/or Refractory Solid Tumor Malignancies

Conditions
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Solid Tumor, Adult, Refractory Cancer

Intervention / Treatment
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* Drug: GV20-0251
* Drug: GV20-0251


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >= 18 years of age previously treated, histologically-confirmed advanced solid malignancy with progressive disease requiring therapy refractory or intolerant to standard therapy(ies) one or more metastatic solid tumors that are evaluable or measurable per RECIST v1.1 ECOG performance status of 0 or 1 Life expectancy of >=12 weeks 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 Exclusion Criteria: Participant with acute luekemia or CLL 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 Known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection 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 Active substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Dose Escalation<br>Part A involves a 3 + 3 dose escalation scheme to evaluate safety and dose limiting toxicities (DLTs) and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GV20-0251. | Drug: GV20-0251<br>* Increasing doses of GV20-0251 given intravenously as monotherapy.<br>|
| Experimental: Part B - Cohort Expansion<br>Part B is a cohort expansion in which eligible participants will be treated at the RP2D of GV20-0251 to further characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of GV20-0251 as well as to evaluate anti-tumor activity in patients with selected malignancies. | Drug: GV20-0251<br>* GV20-0251 RP2D given intravenously as monotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety and tolerability of escalating doses of GV20-0251 in refractory advanced malignancy patients as defined in the protocol during dose escalation | Number of participants with DLTs and Adverse Events (TEAEs, SAEs) | 12 months | 
| Establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of GV20-0251 in participants with advanced and/or specific solid tumor malignancies | Number of participants with DLTs and Adverse Events (TEAEs, SAEs) as well as integration of safety, PD, PK, and preliminary efficacy endpoints. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of area under the plasma concentration-time curve (AUC) of GV20-0251 when given as monotherapy. | Characterize pharmacokinetic (PK) parameter AUC after IV administration of GV20-0251. | 36 months | 
| Measure of maximum plasma concentration (Cmax) of GV20-0251 when given as monotherapy. | Characterize PK parameter Cmax after IV administration of GV20-0251. | 36 months | 
| Measure the time to Cmax (Tmax) of GV20-0251 when given as monotherapy. | Characterize PK parameter Tmax after IV administration of GV20-0251. | 36 months | 
| Measure of Volume of distribution (Vd) of GV20-0251 when given as monotherapy. | Characterize pharmacokinetic (PK) parameter Vd after IV administration of GV20-0251. | 36 months | 
| Measure of terminal half-life (t1/2) of GV20-0251 when given as monotherapy. | Characterize pharmacokinetic (PK) parameter t1/2 after IV administration of GV20-0251. | 36 months | 
| Evaluate the Overall Response Rate (ORR) of GV20-0251. | ORR following GV20-0251 administration is defined as the proportion of efficacy-eligible subjects who have a best response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A responder is defined as any patient who has a best overall response of complete response (CR) or partial response (PR). | 36 months | 
| Evaluate the Progression-free survival (PFS) of GV20-0251. | PFS is defined as the time from the date of study entry (start of treatment) to the first date of objectively determined progressive disease (PD) or death from any cause. | 36 months | 
| Evaluate the Duration of Response (DoR) of GV20-0251. | DoR is defined as the time from the date when the measurement criteria are met for CR or PR (whichever status is recorded first) until the date that recurrence of progressive disease is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). | 36 months | 
| Evaluate the Overall Survival (OS) of GV20-0251. | OS is defined as the time from the date of study entry (signing of ICF) to the date of death from any cause. | 36 months | 
| Evaluate the Disease Control Rate (DCR) of GV20-0251. | DCR following GV20-0251 administration is defined as the proportion of efficacy-eligible subjects who have a best response of complete response (CR), partial response (PR), or stable disease (SD) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | 36 months |