A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0973 in Combination With GDC-0068 When Administered in Participants With Locally Advanced or Metastatic Solid Tumors

Genentech

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Cobimetinib; Drug: Ipatasertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01562275

GE28079

2012-003934-18 (EudraCT Number)

Details and patient eligibility

About

This open-label, multicenter, Phase Ib dose-escalation study will evaluate the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0068 administered in combination in patients with locally advanced or metastatic solid tumors. Cohorts of patients will receive multiple ascending doses of GDC-0973 and GDC-0068. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Enrollment: 67 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically documented locally advanced or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable
• Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
• Life expectancy >/= 12 weeks
• Adequate hematologic and end organ function

Exclusion criteria

• History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment
• History of prior significant toxicity from another phosphoinositide 3-kinase (PI3K) or Akt pathway or mammalian target of rapamycin (mTOR) inhibitor requiring discontinuation of treatment
• Anti-cancer therapy within 28 days prior to first dose of study drug, except as stated in protocol
• History of type I or type II diabetes mellitus requiring insulin
• Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease)
• Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B or hepatitis C virus
• Active autoimmune disease
• Pregnant or lactating women
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• History of glaucoma
• History of retinal vein occlusion

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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67 participants in 3 patient groups

Dose escalation stage 1 (Arm A): Cobimetinib and Ipatasertib

Experimental group

Description:

Participants will receive cobimetinib (GDC-0973) capsules (at a starting dose of 40 mg) and ipatasertib (GDC-0068) capsules (at a starting dose of 200 mg) from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Doses will be increased to identify maximum tolerated dose (MTD) or potential recommended Phase 2 dose (RP2D). Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets.

Treatment:

Drug: Ipatasertib

Drug: Cobimetinib

Dose escalation stage 1 (Arm B): Cobimetinib and Ipatasertib

Experimental group

Description:

Participants will receive cobimetinib (GDC-0973) capsules (at a starting dose of 100 mg) on Days 1, 4, 8, 11, 15, and 18 and ipatasertib (GDC-0068) capsules (at a starting dose of 200 mg) from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Doses will be increased to identify MTD or potential RP2D. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets.

Treatment:

Drug: Ipatasertib

Drug: Cobimetinib

Stage 2 (Indication specific dose expansion cohort)

Experimental group

Description:

Participants will receive cobimetinib (GDC-0973) capsules on Days 1, 4, 8, 11, 15, and 18 and ipatasertib (GDC-0068) capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles, at doses identified as MTD/potential RP2D from Stage 1. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. This indication specific cohort will include participants with phosphatase and tensin homolog (PTEN)-loss triple-negative breast cancer and PTEN-loss endometrial carcinoma.

Treatment:

Drug: Ipatasertib

Drug: Cobimetinib