A Phase 1 Dose Escalation and Expansion Study of GIGA-564, a Minimally Blocking Anti-CTLA-4 Monoclonal Antibody, in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies
Overview
- Phase
- Phase 1
- Intervention
- GIGA-564
- Conditions
- Advanced or Metastatic Solid Tumor Malignancies
- Sponsor
- GigaGen, Inc.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Number of Participants With Grade 3 or 4 TEAEs
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to assess the safety and tolerability of GIGA-564 and identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) level(s) of GIGA-564 in participants with metastatic or locally advanced solid tumor malignancies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide informed consent.
- •Histologically or cytologically confirmed locally advanced or radiographically confirmed metastatic solid tumor malignancies ineligible for standard-of-care or refractory to or relapsing after at least one line of systemic therapy in the metastatic or advanced setting.
- •Measurable disease on imaging as based on Response Evaluation Criteria in RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Life expectancy greater than three months.
- •Electrocardiogram (ECG) without evidence of clinically relevant abnormalities in rhythm, conduction, or morphology of resting ECG or active ischemia as determined by the Investigator.
- •Acceptable organ and marrow function including:
- •Absolute neutrophil count \>= 1,500 cells/ microliters (μL)
- •Platelets \>= 100,000 cells/μL
- •Hemoglobin \>= 9 grams per decilitre (g/dL)
Exclusion Criteria
- •Investigational therapy and/or anti-cancer therapy with the potential for late onset toxicity within 4 weeks or 5 half-lives (whichever is shorter), or nitrosoureas or mitomycin C within 6 weeks. Food and drug administration (FDA)-approved hormonal therapies (e.g., androgen deprivation therapy \[ADT\] for prostate cancer, anti-estrogen for breast cancer, somatostatin analogue for neuroendocrine cancer) are allowed.
- •Failure to resolve toxicity from previous anti-cancer therapy (other than National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v5.0 ≤ Grade 2 alopecia, neuropathy or medically controlled endocrinopathies) to NCI CTCAE v5.0 ≤ Grade
- •Prior receipt of therapy directed against CTLA-
- •Prior receipt of therapy directed against chemokine (C-C motif) receptor 8 (CCR8), cluster of differentiation 25 (CD25), or T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) with an active Fc domain.
- •Baseline prolongation of corrected QT interval (QTc) QT/QTc interval Fridericia's formula (QTcF \> 470 millisecond \[msec\]).
- •History of hepatitis B (HBV) infection unless viral load is undetectable.
- •Participants with known history of hepatitis C (HCV) infection, unless they have been treated and cured (viral load is undetectable).
- •Active or severe infection such as active tuberculosis.
- •Human immunodeficiency virus (HIV) infection unless participants are stable on anti-retroviral therapy (CD4 count ≥ 200/μL) and have a viral load \< 400 copies/mL.
- •Significant cardiovascular disease (such as New York Heart Association Class II or greater heart failure), myocardial infarction within 3 months prior to initiation of study treatment, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
Arms & Interventions
GIGA-564: Dose Escalation (Phase 1A)
Up to 5 dose levels \[0.3, 1.0, 3.0, 10.0, and 20.0 milligrams per kilogram (mg/kg)\] will be evaluated sequentially. Participants will receive GIGA-564 intravenously over at least 60 minutes on Day 1 of every 3 weeks (3 weeks = 1 cycle) for up to 4 cycles until time of confirmed disease progression, unacceptable toxicity, or other reason for treatment discontinuation.
Intervention: GIGA-564
GIGA-564: Dose Expansion (Phase 1B)
Dose expansion (Phase 1B) of selected dose levels may be initiated following the preliminary clearance of those specified dose levels from the dose escalation (Phase 1A) as determined by the Sponsor and SRC. Participants will receive up to 4 cycles of one of up to three tolerable dose levels of GIGA-564. GIGA-564 will be given intravenously over at least 60 minutes on Day 1 of every 3 weeks (3 weeks = 1 cycle) for up to 4 cycles until time of confirmed disease progression, unacceptable toxicity, or other reason for treatment discontinuation.
Intervention: GIGA-564
Outcomes
Primary Outcomes
Number of Participants With Grade 3 or 4 TEAEs
Time Frame: Up to 154 days
Number of Participants With Treatment-related TEAEs
Time Frame: Up to 154 days
Number of Participants With Dose-limiting Toxicities (DLTs) during Cycle 1
Time Frame: Up to 21 days
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to 154 days
Number of Participants With Grade 3 or 4 Treatment-related TEAEs
Time Frame: Up to 154 days
Number of Participants With Serious Adverse Events (SAE's)
Time Frame: Up to 154 days
Number of Participants Who Discontinued Treatment due to Adverse Events (AEs)
Time Frame: Up to 154 days
Secondary Outcomes
- Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Up to Week 24)
- Percentage of Participants with Minor RECIST 1.1 Response(Up to Week 24)
- Disease Control Rate (DCR) per RECIST 1.1(Up to Week 24)
- Progression Free Survival (PFS)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)
- Area Under the Serum Concentration-time Curve during a Dosage Interval (AUC0-tau) of GIGA-564 during Cycle 1 and Cycle 4(Up to 84 days)
- Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC[0-inf)] of GIGA-564 during Cycle 1(Up to 21 days)
- Maximum Observed Serum concentration (Cmax) of GIGA-564 during Cycle 1 and Cycle 4(Up to 154 days)
- Time to Reach Maximum Observed Serum Concentration (Tmax) of GIGA-564 during Cycle 1 and Cycle 4(Up to 154 days)
- Trough Observed Serum Concentration (C trough) of GIGA-564 during Cycle 1 and Cycle 4(Up to 154 days)
- Elimination Half-life (t1/2) of GIGA-564 during Cycle 1 and Cycle 4(Up to 154 days)
- Apparent Total Body Clearance (CL) of GIGA-564 during Cycle 1(Up to 21 days)
- Volume of Distribution at Steady State (Vss) of GIGA-564 during Cycle 1(Up to 21 days)
- Accumulation Ratio for Maximum Observed Serum Concentration (Cmax) of GIGA-564(Up to 154 days)
- Accumulation Ratio for Trough Observed Serum Concentration (Ctrough) of GIGA-564(Up to 154 days)
- Accumulation Ratio for Area Under the Serum Concentration-time Curve (AUC) of GIGA-564(Up to 154 days)