A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 as a Single Agent and in Combination With Checkpoint Inhibitor in Participants With Locally Advanced or Metastatic Solid Tumors

Genentech

Status and phase: Enrolling; Phase 1

Conditions: Clear Cell RCC; Melanoma; Esophageal Cancer; Urothelial Carcinoma; HNSCC; HCC; Locally Advanced or Metastatic Solid Tumors; Gastric Cancer; TNBC; Cervical Cancer; Colorectal Cancer; NSCLC

Treatments: Drug: RO7502175; Drug: Pembrolizumab; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05581004

2021-006708-34 (EudraCT Number)

GO43860

Details and patient eligibility

About

This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of RO7502175 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.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Life expectancy 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 (RECIST) Version 1.1
• 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 RO7501275, 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, or radiotherapy, within 3 weeks prior to initiation of study treatment
• Active hepatitis B or C 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 RO7502175 infusion
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Active or history of autoimmune disease
• Prior allogeneic stem cell or organ transplantation

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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450 participants in 4 patient groups

Phase Ia: Dose Escalation

Experimental group

Description:

Participants in successive cohorts will receive escalating doses of RO7502175, as an intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: RO7502175

Phase Ia: Expansion

Experimental group

Description:

Participants with select solid tumors will receive a recommended dose of RO7502175, determined in Phase Ia Dose Escalation phase as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: RO7502175

Phase Ib: Dose Escalation

Experimental group

Description:

Participants in successive cohorts will receive escalating doses of RO7502175, as an IV infusion, in combination with a fixed dose of atezolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Atezolizumab

Drug: RO7502175

Phase Ib: Expansion

Experimental group

Description:

Participants with select solid tumors will receive a recommended dose of RO7502175, determined in Phase Ib Dose Escalation phase, as an IV infusion, in combination with a fixed dose of atezolizumab or pembrolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Atezolizumab

Drug: Pembrolizumab

Drug: RO7502175