A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation

Genentech

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumors; Colorectal Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: Inavolisib; Drug: Atezolizumab; Drug: Bevacizumab; Drug: GDC-1971; Drug: GDC-6036; Drug: Cetuximab; Drug: Erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04449874

GO42144

2023-506311-18-00 (Other Identifier)

2020-000084-22 (EudraCT Number)

Details and patient eligibility

About

This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.

Enrollment: 498 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically documented advanced or metastatic solid tumor with KRAS G12C mutation.
• Women of childbearing potential must agree to remain abstinent or use contraception, and agree to refrain from donating eggs during the treatment period and after the final dose of study treatment as specified in the protocol.
• Men who are not surgically sterile must agree to remain abstinent or use a condom, and agreement to refrain from donating sperm during the treatment period and after the final dose of study treatment as specified in the protocol.

Exclusion criteria

• Active brain metastases.
• Malabsorption or other condition that interferes with enteral absorption.
• Clinically significant cardiovascular dysfunction or liver disease.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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498 participants in 7 patient groups

Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II)

Experimental group

Description:

Participants in Stage I will receive GDC-6036 administered orally once daily (PO QD). The dose will be increased in successive cohorts until a study-specific threshold is reached. Participants with select solid tumors will be treated with GDC-6036 PO QD in Stage II.

Treatment:

Drug: GDC-6036

Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II)

Experimental group

Description:

Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab.

Treatment:

Drug: GDC-6036

Drug: Atezolizumab

Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)

Experimental group

Description:

Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.

Treatment:

Drug: Cetuximab

Drug: GDC-6036

Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)

Experimental group

Description:

Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.

Treatment:

Drug: GDC-6036

Drug: Bevacizumab

Arm E: GDC-6036 + Erlotinib (Stage I and Stage II)

Experimental group

Description:

Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib.

Treatment:

Drug: Erlotinib

Drug: GDC-6036

Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II)

Experimental group

Description:

Participants with solid tumors will receive GDC-6036 in combination with GDC-1971 PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with GDC-1971 PO in Stage II.

Treatment:

Drug: GDC-6036

Drug: GDC-1971

Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)

Experimental group

Description:

Participants with solid tumors will receive GDC-6036 in combination with inavolisib PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with inavolisib PO in Stage II.

Treatment:

Drug: GDC-6036

Drug: Inavolisib