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
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.
Arms & interventions
- BiologicalGV20-0251
Increasing doses of GV20-0251 administered by intravenous (IV) infusion once or twice every 3 weeks as monotherapy.
- BiologicalGV20-0251
GV20-0251 preliminary RP2D administered by IV infusion 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.
- BiologicalGV20-0251 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.
Outcome measures
Primary
Objective Response Rate ORR per RECIST version 1.1 (Parts B and D)
ORR
Time frame: 12 months
Percentage of Participants With Adverse Events (Parts A and C)
Time frame: 12 months
Secondary
Overall Survival (Parts B and D)
Time frame: 24 months
Additional safety and tolerability
Time frame: 24 months
Cmax of GV20-0251
Time frame: 12 months
Tmax of GV20-0251
Time frame: 12 months
T1/2
Time frame: 12 months
AUC
Time frame: 12 months
ADAs
Time frame: 12 months
nADAs
Time frame: 12 months
DCR
Time frame: 24 months
DoR
Time frame: 24 months
PFS
Time frame: 24 months
ORR (Parts A and C)
Time frame: 24 months
Eligibility criteria
Study locations (13)
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
HealthONE Clinic Services Oncology - Hematology, LLC d/b/a Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Yale University
New Haven, Connecticut, 06511
Florida Cancer Specialists & Research Institute, LLC
Fort Myers, Florida, 33916
Community Health Network, Inc.
Indianapolis, Indiana, 46256
Massachusetts General Hospital
Boston, Massachusetts, 02114
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
Detroit, Michigan, 48201
NYU Langone Health
New York, New York, 10016
Oregon Health & Science University
Portland, Oregon, 97239
Verdi Oncology Tennessee, Scri Oncology Partners
Nashville, Tennessee, 37203
Oncology Consultants, P.A.
Houston, Texas, 77030
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Virginia Cancer Specialists
Fairfax, Virginia, 22031
References
- Li Y, Wu X, Sheng C, Liu H, Liu H, Tang Y, Liu C, Ding Q, Xie B, Xiao X, Zheng R, Yu Q, Guo Z, Ma J, Wang J, Gao J, Tian M, Wang W, Zhou J, Jiang L, Gu M, Shi S, Paull M, Yang G, Yang W, Landau S, Bao X, Hu X, Liu XS, Xiao T. IGSF8 is an innate immune checkpoint and cancer immunotherapy target. Cell. 2024 May 23;187(11):2703-2716.e23. doi: 10.1016/j.cell.2024.03.039. Epub 2024 Apr 23.(PubMed)
- Wentzel, K., Peguero, J., Kummar, S., Lorusso, P., Mehnert, J. M., Spira, A. I., Naing, A., Hamid, O., Mehmi, I., Benhadji, K., Alland, L., Hu, X., Xiao, H., Bao, X., Chen, J., Gong, Y., Liu, X. S. ESMO 2024