Advanced Solid Tumor
Conditions
Brief summary
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of denikitug (also known as GS-1811) as monotherapy and in combination with zimberelimab in participants with advanced solid tumors. This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.
Detailed description
Part D allocation for 1 cohort will be randomized.
Interventions
DRUGDenikitug
Administered Intravenously
DRUGZimberelimab
Administered Intravenously
Sponsors
Gilead Sciences
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
Key Inclusion Criteria: * Disease: * Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit. * Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit. * Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-\[L\]1) monoclonal antibody monotherapy. * Part D: Individuals with pathologically confirmed select advanced solid tumors. * Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit. * Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F. * Adequate organ function. * Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception. * Tissue requirement: * Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment. * Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis. Key
Exclusion criteria
* Concurrent anticancer treatment. * Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (\< 28 days), chemotherapy (\< 21 days), targeted small molecule therapy (\< 14 days), hormonal therapy or other adjunctive therapy (\< 14 days) or radiotherapy (\< 21 days). * Any prior CCR8 directed therapy. * Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed. * Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for \> 2 years. * History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy. * History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years. * History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis). * Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics. * Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). * Positive serum pregnancy test or breastfeeding female. * Live vaccines within 30 days prior to first dose. * Significant cardiovascular disease. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C | Day 1 Through Day 21 |
| Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days |
| Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0 | First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Area Under the Concentration-time Curve (AUC) for Denikitug | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | — |
| Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | — |
| Objective response rate (ORR) in Part D | Day 1 Up to End of Treatment (24 months) | Objective response rate is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
| Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | — |
| Time to response (TTR) | Day 1 Up to End of Treatment (24 months) | Time to response is defined as the time from the first dose of Denikitug in combination with Zimberelimab to the first documentation of CR or PR that is subsequently confirmed |
| Duration of response (DOR) | Day 1 Up to End of Treatment (24 months) | Duration of response is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause, if applicable. |
| Progression-free survival (PFS) | Day 1 Up to End of Treatment (24 months) | Progression-free survival is defined as the time from the first dose of Denikitug in combination with Zimberelimab to the earlier of the first documentation of definitive PD or death from any cause |
| Disease control rate (DCR) | Day 1 Up to End of Treatment (24 months) | Disease control rate is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) as assessed by RECIST Version 1.1 |
| PK Parameter: Minimum Observed Concentration (Cmin) for Denikitug | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | — |
| PK Parameter: Time of Maximum Observed Concentration (Tmax) for Denikitug | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | — |
Countries
Australia, Canada, Spain, Taiwan, United States
Contacts
Primary ContactGilead Clinical Study Information Center
Outcome results
None listed