A Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of GDC-0032 in Combination With Docetaxel or With Paclitaxel in Patients With HER2-negative Locally Recurrent or Metastatic Breast Cancer or Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral GDC-0032 administered in combination with either docetaxel or with paclitaxel. Patients treated with the GDC-0032 and docetaxel have HER2-negative locally recurrent or metastatic breast cancer or non-small cell lung cancer (NSCLC). Patients treated with the GDC-0032 and paclitaxel combination have human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer. There are two potential stages within each arm of this study: a dose-escalation stage (Stage 1) and a dose-expansion stage (Stage 2). Once the maximum tolerated dose of GDC-0032 in a given arm has been established from dose escalation, additional patients with each combination will be enrolled in Stage 2.

Conditions
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Breast Cancer, Non-small Lung Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: GDC-0032
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years For paclitaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease For docetaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease or histologically documented advanced (Stage IV) or recurrent NSCLC For participants with breast cancer: HER2-negative disease as defined by local clinical guidelines Participants with NSCLC to be treated with docetaxel need to have received at least one prior anti-cancer treatment regimen in an advanced setting and to have docetaxel be considered appropriate treatment Evaluable or measurable disease per response evaluation criteria in solid tumors (RECIST) v.1.1 Life expectancy >=12 weeks Eastern cooperative oncology group (ECOG) performance status of 0 or 1 at screening Adequate hematologic and end organ function Use of highly effective form of contraception Exclusion Criteria: Prior anti-cancer therapy Prior treatment with phosphoinositide 3-kinase (PI3K) inhibitor Known significant hypersensitivity to any components of study treatment Grade >=2 peripheral neuropathy Type 1 or Type 2 diabetes Grade >=2 hypercholesterolemia or hypertriglyceridemia Congenital long QT syndrome Active congestive heart failure or ventricular arrhythmia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: GDC-0032 + Docetaxel<br>Participants will receive GDC-0032 once daily for 21 consecutive days (beginning from Day 1) in each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. | Drug: Docetaxel<br>* Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.<br>Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>|
| Experimental: Arm B: GDC-0032 + Paclitaxel<br>Participants will receive GDC-0032 once daily for 28 consecutive days (beginning from Day 1) in each 28-day cycle along with Paclitaxel on Days 1, 8, 15 and 22 of each 28-day cycle. | Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>Drug: Paclitaxel<br>* Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.<br>|
| Experimental: Arm C: GDC-0032 + Docetaxel<br>Participants will receive GDC-0032 once daily on Day 1 and Days 8-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. | Drug: Docetaxel<br>* Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.<br>Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>|
| Experimental: Arm D: GDC-0032 + Docetaxel<br>Participants will receive GDC-0032 once daily on Days 2-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. | Drug: Docetaxel<br>* Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.<br>Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>|
| Experimental: Arm E: GDC-0032 + Docetaxel<br>Participants will receive GDC-0032 once daily on Days 1-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. | Drug: Docetaxel<br>* Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.<br>Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>|
| Experimental: Arm F: GDC-0032 + Paclitaxel<br>Participants will receive GDC-0032 once daily on a 5-days on, 2-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle. | Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>Drug: Paclitaxel<br>* Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.<br>|
| Experimental: Arm G: GDC-0032 + Paclitaxel<br>Participants will receive GDC-0032 once daily on a 3-days on, 4-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle. | Drug: GDC-0032<br>* Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.<br>Drug: Paclitaxel<br>* Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | Approximately 3 years | 
| Safety: Incidence of dose limiting toxicities |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from time 0 to the last measurable concentration (AUC0-last) |  | Up to 28 days | 
| Time to maximum observed plasma concentration (Tmax) |  | Up to 28 days | 
| Maximum observed plasma concentration (Cmax) |  | Up to 28 days | 
| Minimum observed plasma concentration (Cmin) |  | Up to 28 days | 
| Objective response according to RECIST v1.1 |  | Approximately 3 years | 
| Duration of response according to RECIST v1.1 |  | Approximately 3 years | 
| Progression-free survival (PFS) according to RECIST v1.1 |  | Approximately 3 years |