Clinical trial NCT05669430: A Study of GV20-0251 Monotherapy and GV20-0251 in Combination With Pembrolizumab in Participants With Solid Tumor Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: GV20-0251
Lead sponsor: GV20 Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-12-30
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate ORR per RECIST version 1.1 (Parts B and D)
timeFrame: 12 months
measure: Percentage of Participants With Adverse Events (Parts A and C)
timeFrame: 12 months
Secondary outcomes:
measure: Overall Survival (Parts B and D)
timeFrame: 24 months
measure: Additional safety and tolerability
timeFrame: 24 months
measure: Cmax of GV20-0251
timeFrame: 12 months
measure: Tmax of GV20-0251
timeFrame: 12 months
measure: T1/2
timeFrame: 12 months
measure: AUC
timeFrame: 12 months
measure: ADAs
timeFrame: 12 months
measure: nADAs
timeFrame: 12 months
measure: DCR
timeFrame: 24 months
measure: DoR
timeFrame: 24 months
measure: PFS
timeFrame: 24 months
measure: ORR (Parts A and C)
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Denver
country: United States
facility: HealthONE Clinic Services Oncology - Hematology, LLC d/b/a Sarah Cannon Research Institute at HealthONE
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists & Research Institute, LLC
state: Florida
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
state: Michigan
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Verdi Oncology Tennessee, Scri Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: The University of Texas M. D. Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References:
citation: 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.
citation: 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