Cervical Cancer, Clear Cell RCC, Colorectal Cancer, Esophageal Cancer, Gastric Cancer, HCC, HNSCC, Locally Advanced or Metastatic Solid Tumors, Melanoma, NSCLC, TNBC, Urothelial Carcinoma
Conditions
Brief summary
This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of enzelkitug when administered as a single agent and in combination with atezolizumab or pembrolizumab in adult participants with locally advanced or metastatic solid tumors, including non small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, triple-negative breast cancer (TNBC), esophageal cancer, gastric cancer, cervical cancer, colorectal cancer (CRC), urothelial carcinoma (UC), clear cell renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Participants will be enrolled in 2 stages: dose escalation and dose expansion.
Interventions
DRUGPembrolizumab
Pembrolizumab will be administered as per the schedule specified in the respective arms.
DRUGEnzelkitug
Enzelkitug will be administered as per the schedule specified in the respective arms.
DRUGAtezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arms.
Sponsors
Genentech, Inc.
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
* Life expectancy of at least 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) * Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy * Tumor specimen availability
Exclusion criteria
* Pregnant or breastfeeding or intention of becoming pregnant during the study or within 4 months after the final dose of enzelkitug, or 4 months after the final dose of pembrolizumab, or 5 months after the final dose of atezolizumab * Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study treatment * Active hepatitis B (HBV) or hepatitis C (HCV) or tuberculosis * Positive test for human immunodeficiency virus (HIV) infection * Acute or chronic active Epstein-Barr virus (EBV) infection at screening * Administration of a live, attenuated vaccine (e.g., FluMist) within 4 weeks before first enzelkitug infusion * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * Active or history of autoimmune disease * Prior allogeneic stem cell or organ transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ia: Number of Participants With Dose-limiting Toxicities (DLTs) | From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment) (1 Cycle=21 days) |
| Phase Ib: Number of Participants With DLTs | From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment) (1 Cycle=21 days) |
| Phase Ia: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 52 months |
| Phase Ib: Number of Participants With TEAEs | Up to approximately 52 months |
Secondary
| Measure | Time frame |
|---|---|
| Phase Ia and Phase Ib: Maximum Serum Concentration (Cmax) of Enzelkitug | From Cycle 1 (each cycle is 21 days) Day 1, and at multiple timepoints up to each follow-up visits (up to approximately 52 months) |
| Phase Ia and Phase Ib: Objective Response Rate (ORR) | From Cycle 1(each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 52 months) |
| Phase Ia and Phase Ib: Duration of Response (DOR) | From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 52 months) |
| Phase Ia and Phase Ib: Progression-free Survival (PFS) | From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 52 months) |
| Phase Ia and Phase Ib: Percentage of Participants With Anti-drug Antibody (ADA) to Enzelkitug | From Cycle 1 (each cycle is 21 days) Day 1, and at multiple timepoints up to treatment discontinuation (up to approximately 52 months) |
Countries
Australia, Belgium, Canada, Greece, Netherlands, South Korea, Spain, Sweden, Taiwan, United States
Contacts
STUDY_DIRECTORClinical Trials
Genentech, Inc.
Outcome results
None listed