A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors

Genentech

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: GDC-0919; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02471846

2015-001741-88 (EudraCT Number)

GO29779

Details and patient eligibility

About

This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.

Enrollment: 158 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy at least 12 weeks
• Adequate hematologic and end organ function
• Negative pregnancy test and willingness to utilize contraception among women of childbearing potential
• Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1
• Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care
• For the expansion stage, histologically confirmed renal cell cancer (RCC), urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma (HNSCC), gastric cancer, ovarian cancer, cervical cancer, endometrial cancer, or Merkel cell cancer
• For the expansion stage, evaluable for PD-L1 expression
• Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled

Exclusion criteria

• Significant cardiovascular or liver disease
• Major surgery within 28 days of study drug
• Any anti-cancer therapy within 3 weeks of study drug
• Malabsorption syndrome or poor upper gastrointestinal integrity
• Primary central nervous system (CNS) malignancy or active metastases within 5 years
• Uncontrolled tumor pain
• Autoimmune disease other than stable hypothyroidism or vitiligo
• Human immunodeficiency virus (HIV), active hepatitis B or C, or tuberculosis
• Signs/symptoms of infection, or use of antibiotics within 2 weeks of study drug
• Live attenuated vaccine within 4 weeks of study drug
• Known history or predisposition to QT interval prolongation
• Prior cancer immunotherapy, specifically indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) inhibitors, T-cell costimulatory receptor agonist antibodies, or checkpoint inhibitors among certain participants

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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158 participants in 6 patient groups

Anti-PD-1/PD-L1 Relapsed Cohort I

Experimental group

Description:

Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Treatment:

Drug: Atezolizumab

Drug: GDC-0919

Anti-PD-1/PD-L1 Relapsed Cohort II

Experimental group

Description:

Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Treatment:

Drug: Atezolizumab

Drug: GDC-0919

Biopsy Cohort A

Experimental group

Description:

Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Treatment:

Drug: Atezolizumab

Drug: GDC-0919

Biopsy Cohort B

Experimental group

Description:

Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Treatment:

Drug: Atezolizumab

Drug: GDC-0919

Dose-Escalation Cohort(s)

Experimental group

Description:

Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage.

Treatment:

Drug: Atezolizumab

Drug: GDC-0919

Expansion Cohorts

Experimental group

Description:

Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Treatment:

Drug: Atezolizumab

Drug: GDC-0919