A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

An Open-Label, Phase I/II, Dose-Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma and in Combination With Endocrine Therapy in Patients With Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01296555
• Other study ID #: PMT4979g
• Secondary ID: GO008862012-0020
• Status: Completed
• Phase: Phase 1
• Start date: March 16, 2011
• Est. completion date: June 25, 2021

Study information

• Verified date: September 2021
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, Phase I/II study to assess the safety, tolerability, and pharmacokinetics of GDC-0032. The Phase I portion will be divided into two stages. During Stage 1, GDC-0032 will be administered every day orally and at escalating doses in participants with locally advanced or metastatic solid tumors. During Stage 2, GDC-0032 will be administered alone or as combination therapy within indication-specific cohorts. In Phase II of the study, the efficacy and safety of the combination GDC-0032 and fulvestrant will be evaluated in post-menopausal female participants with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, hormone receptor-positive breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 686
• Est. completion date: June 25, 2021
• Est. primary completion date: June 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Phase I (Cohorts A through D, G, H, T, T2 and X): Histologically documented, locally advanced or metastatic solid malignancy or NHL that has progressed or failed to respond to at least one prior regimen and are not candidates for regimens known to provide clinical benefit

• Phase I (Cohorts E and F): Post-menopausal females with locally advanced or metastatic hormone receptor-positive breast cancer that has progressed or failed to respond to at least one prior endocrine therapy in the adjuvant or metastatic setting

• Phase I (Cohorts J through S): Post-menopausal females with HER2-negative, hormone-receptor positive breast cancer that has progressed or failed to response to at least one prior endocrine therapy in the adjuvant or metastatic setting

• Phase II: Post-menopausal female participants with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer

• Phase I (Cohorts A through S) and Phase II: Evaluable or measurable disease per RECIST version 1.1

• Phase I (Cohorts T, and T2): Greater than or equal to (>/=) 1 bi-dimensionally measurable lesion on computed tomography (CT) scan

• Phase I (Cohort T): Participants with non-Hodgkin's lymphoma, regardless of PIK3CA mutation status

• Phase 1 (Cohort T2): Participants with diffuse large B-cell lymphoma (DLBCL), regardless of PIK3CA mutation status

• Phase I (Cohort X): Participants with PIK3CA-mutant tumors and measurable disease per RECIST v1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at Screening

• Life expectancy of >/= 12 weeks

• Adequate hematologic and organ function within 28 days prior to initiation of study treatment

• Documented willingness to use an effective means of contraception for both men and women while participating in the study

Exclusion Criteria:

• Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring treatment)

• Active congestive heart failure or ventricular arrhythmia requiring medication

• Participants requiring any daily supplemental oxygen

• Active inflammatory disease requiring immunosuppressants, including small or large intestinal inflammation such as Crohn's disease or ulcerative colitis

• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

• Treatment with chemotherapy less than or equal to (</=) 3 weeks before study treatment

• Oral endocrine therapy </= 2 weeks before study treatment

• Treatment with investigational drug </= 3 weeks or 5 half-lives before study treatment

• Treatment with biologic therapy </= 3 weeks before study treatment

• Treatment with kinase inhibitors </= 2 weeks before study treatment

• Radiation therapy (other than radiation to bony metastases) as cancer therapy </= 4 weeks before study treatment

• Palliative radiation therapy to bony metastases </= 2 weeks before study treatment

• Major surgery </= 4 weeks before study treatment

• Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participant at high risk from treatment complications (examples include but are not limited to clinically significant non-healing wound, active bleeding, or ongoing fistula or active tuberculosis infection)

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma
• Solid Cancers

Intervention

Drug:
• Fulvestrant
Participants will receive fulvestrant 500 milligrams (mg) via intramuscular injection (as per package insert or Summary of Product Characteristics [SmPC]) on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent cycle, until disease progression (Cycle length: 28 days).
• GDC-0032
Participants will receive GDC-0032 at escalating (Phase I, Stage 1) or fixed (Phase II and Phase I, Stage 2) doses until disease progression. Cycle 1 may be 35 days in length to allow for a 7-day washout following the initial dose; thereafter, GDC-0032 will be administered orally once daily in 28-day cycles.
• Letrozole
Participants will receive letrozole 2.5 mg orally (as per Package Insert or SmPC) once daily in 28-day cycles until disease progression.
• Midazolam
Participants will receive midazolam 5 mg (as per Package Insert or SmPC) in hydrochloride syrup on Days 1 and 16 of Cycle 1.

Locations

Country	Name	City	State
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
France	Institut Gustave Roussy	Villejuif
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Texas Cancer Center	Abilene	Texas
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Dana Farber Cancer Inst.	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Univ of Chicago	Chicago	Illinois
United States	Baylor Sammons Cancer Center	Dallas	Texas
United States	Mary Crowley Cancer Rsch Ctr	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Florida Cancer Specialists - Fort Myers (New Hampshire Ct)	Fort Myers	Florida
United States	West Cancer Center	Germantown	Tennessee
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Res Inst; TN Onc	Nashville	Tennessee
United States	Vanderbilt	Nashville	Tennessee
United States	Vanderbilt Breast Center; Vanderbilt Health Pharmacy	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Sarah Cannon Res Inst; OK	Oklahoma City	Oklahoma
United States	University of California Irvine Medical Center	Orange	California
United States	UC Davis; Comprehensive Cancer Center	Sacramento	California
United States	Washington University; Division of Oncology	Saint Louis	Missouri
United States	Sutter Health	San Francisco	California
United States	Sarah Cannon Res Inst; FL	Sarasota	Florida
United States	TGen Clinical Research Srvs	Scottsdale	Arizona
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	USO - Tyler Cancer Ctr	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver	Vancouver	Washington
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I Stage I: Percentage of Participants With Adverse Events and Serious Adverse Events		Baseline up to approximately 5 years
Primary	Phase 1 Stage 1: Percentage of Participants With Dose-Limiting Toxicities		Baseline up to 35 days
Primary	Phase I Stage 1: Maximum Tolerated Dose of GDC-0032		Baseline up to 35 days
Primary	Phase I: Area Under the Concentration-Time Curve (AUC) From Zero to Infinity of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hours [hr]), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr);1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22;thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2,Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15;Predose (0-2 hr) on Cycle 1 Days 8, 16;thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days)	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: AUC From Zero to tau (AUCtau) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Maximum Observed Concentration (Cmax) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Minimum Observed Concentration (Cmin) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Time to Reach Cmax (tmax) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Half-life (t1/2) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Apparent Clearance (CL/F) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Accumulation Ratio (AR) (Area Under the Concentration Time Curve at Steady-State Divided by Area Under the Concentration Time Curve for First Dose) of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Primary	Phase I: Recommended Dose of Single-Agent GDC-0032		Baseline up to 35 days
Primary	Phase II: Percentage of Participants With Clinical Benefit, as Assessed Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Primary	Phase II: Percentage of Participants With Objective Response, as Assessed Using RECIST Version 1.1		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I: Fraction Dose Excreted (fe) of GDC-0032		Urine samples: Predose (0 hr), 0-6 hr and 6-24 hr after dosing on Day 1 of Cycle 1 (cycle length: 35 days)
Secondary	Phase I: Renal Clearance (CLr) of GDC-0032		Urine samples: Predose (0 hr), 0-6 hr and 6-24 hr after dosing on Day 1 of Cycle 1 (cycle length: 35 days)
Secondary	Phase I: Time to Achieve Steady State of GDC-0032	Detailed timeframe: Stage 1: Predose (0-2 hr), 0.5, 1, 2, 3, 4, 8, 24 (Days 1 and 15), 48, 72 hr (Day 1 only) postdose, Cycle 1; Predose (0-2 hr) on Days 8, 22, 29 of Cycle 1 and on Day 1 of each subsequent cycle up to Study Completion/Early Termination (approximately 5 years) (cycle length: 35 days for Cycle 1, 28 days for other cycles).; Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts B, D, G: Predose (0-2 hr), 3 hr postdose on Cycle 1 Days 1, 15; Predose (0-2 hr) on Cycle 1 Days 8, 16; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days).; Stage 2, Cohorts H, T, T2, X: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (Detailed cohort-wise timeframe is given in the description)
Secondary	Phase I All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response, as Assessed Using RECIST Version 1.1		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I All Cohorts (Except Cohorts T and T2): Duration of Objective Response, as Assessed Using RECIST Version 1.1		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I All Cohorts (Except Cohorts T and T2): Progression Free Survival, as Assessed Using RECIST Version 1.1		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Cohort T: Percentage of Participants With Best Overall Response, as Assessed Using 2007 Revised International Working Group (IWG) Response Criteria in Malignant Lymphoma		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Cohort T: Duration of Objective Response, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Cohort T: Progression Free Survival, as Assessed Using 2007 Revised IWG Response Criteria in Malignant Lymphoma		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Cohort T2: Percentage of Participants With Best Overall Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Cohort T2: Duration of Objective Response, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Cohort T2: Progression Free Survival, as Assessed Using Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma		Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Secondary	Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fed Condition		Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days)
Secondary	Phase I Stage 2 Food Effect: Cmax of GDC-0032 Under Fasted Condition		Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days)
Secondary	Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fed Condition		Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days)
Secondary	Phase I Stage 2 Food Effect: AUC of GDC-0032 Under Fasted Condition		Stage 2, Cohort A: Predose (0-2 hr); 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Days 1, 8, 22; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (approximately 5 years) (Cycle length: 28 days)
Secondary	Phase I Stage 2 Cohort C: AUC from Time Zero to 24 Hours (AUC0-24) of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing		Predose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose on Cycle 1 Days 1 and 16 (Cycle length: 28 days)
Secondary	Phase I Stage 2 Cohort C: Cmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing		Predose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose on Cycle 1 Days 1 and 16 (Cycle length: 28 days)
Secondary	Phase I Stage 2 Cohort C: Tmax of Midazolam Prior to and After 14 Days Continuous GDC-0032 Dosing		Predose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose on Cycle 1 Days 1 and 16 (Cycle length: 28 days)
Secondary	Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of Letrozole	Detailed timeframe: Stage 2 Cohort E: Predose (0-2 hr) on Cycle 1 Day 1; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohort N, P, Q, R: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).; Stage 2 Cohort S: Predose (0-4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of Letrozole	Detailed timeframe: Stage 2 Cohort E: Predose (0-2 hr) on Cycle 1 Day 1; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohort N, P, Q, R: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).; Stage 2 Cohort S: Predose (0-4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts E, N, P, Q, R, S: tmax of Letrozole	Detailed timeframe: Stage 2 Cohort E: Predose (0-2 hr) on Cycle 1 Day 1; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohort N, P, Q, R: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).; Stage 2 Cohort S: Predose (0-4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of Fulvestrant	Detailed timeframe: Stage 2 Cohort F: Predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohorts J, K, M: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).; Stage 2 Cohort L: Predose (0-4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).; Phase II: Predose (0-4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of Fulvestrant	Detailed timeframe: Stage 2 Cohort F: Predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohorts J, K, M: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).; Stage 2 Cohort L: Predose (0-4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).; Phase II: Predose (0-4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: tmax of Fulvestrant	Detailed timeframe: Stage 2 Cohort F: Predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohorts J, K, M: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).; Stage 2 Cohort L: Predose (0-4 hr) on Day 1 of Cycle 2, 6 (Cycle length: 28 days).; Phase II: Predose (0-4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohort C: AUC0-24 of GDC-0032 in Combination with Midazolam		Predose (0-2 hr), on Day 2, 16 Cycle 1; 0.5, 1,1.5, 2, 3, 4, 8, 24 hr post-dose on Day 16 Cycle 1; thereafter predose (0-2 hr) on Day 1 of each Cycles up to study completion/early termination (up to approximately 5 years) (cycle length: 28 days)
Secondary	Phase I Stage 2 Cohort C: Cmax of GDC-0032 in Combination with Midazolam		Predose (0-2 hr), on Day 2, 16 Cycle 1; 0.5, 1,1.5, 2, 3, 4, 8, 24 hr post-dose on Day 16 Cycle 1; thereafter predose (0-2 hr) on Day 1 of each Cycles up to study completion/early termination (up to approximately 5 years) (cycle length: 28 days)
Secondary	Phase I Stage 2 Cohort C: Tmax of GDC-0032 in Combination with Midazolam		Predose (0-2 hr), on Day 2, 16 Cycle 1; 0.5, 1,1.5, 2, 3, 4, 8, 24 hr post-dose on Day 16 Cycle 1; thereafter predose (0-2 hr) on Day 1 of each Cycles up to study completion/early termination (up to approximately 5 years) (cycle length: 28 days)
Secondary	Phase I Stage 2 Cohorts E, N, P, Q, R, S: AUC0-24 of GDC-0032 in Combination with Letrozole	Detailed timeframe: Stage 2 Cohort E: Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each Cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohort N, P, Q, R: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).; Stage 2 Cohort S: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts E, N, P, Q, R, S: Cmax of GDC-0032 in Combination with Letrozole	Detailed timeframe: Stage 2 Cohort E: Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each Cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohort N, P, Q, R: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).; Stage 2 Cohort S: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts E, N, P, Q, R, S: Tmax of GDC-0032 in Combination with Letrozole	Detailed timeframe: Stage 2 Cohort E: Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each Cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohort N, P, Q, R: Predose (0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).; Stage 2 Cohort S: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: AUC0-24 of GDC-0032 in Combination with Fulvestrant	Detailed timeframe: Stage 2 Cohort F:Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohorts J, K, M: Predose(0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).; Stage 2 Cohort L: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Cmin of GDC-0032 Fulvestrant	Detailed timeframe: Stage 2 Cohort F:Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohorts J, K, M: Predose(0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).; Stage 2 Cohort L: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately approximately 5 years (detailed timeframe is given in description)
Secondary	Phase I Stage 2 Cohorts F, J, K, L, M and Phase II: Tmax of GDC-0032 Fulvestrant	Detailed timeframe: Stage 2 Cohort F:Predose (0-2 hr), 3 hr postdose on Cycle 1 Day 1; Predose (0-2 hr) on Cycle 1 Day 8; Predose (0-2 hr), 1, 2, 3, 4, 8, 24 hr postdose on Cycle 1 Day 15; thereafter predose (0-2 hr) on Day 1 of each cycle up to study completion/early termination (up to approximately 5 years) (Cycle length: 28 days).; Stage 2 Cohorts J, K, M: Predose(0-4 hr) on Day 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).; Stage 2 Cohort L: 3 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days).	Baseline up to approximately approximately 5 years (detailed timeframe is given in description)
Secondary	Phase II: Duration of Objective Response, as Assessed Using RECIST Version 1.1		Baseline up to disease progression or death, whichever occurred first (up to approximately 5 years)
Secondary	Phase II: Progression Free Survival, as Assessed Using RECIST Version 1.1		Baseline up to disease progression or death, whichever occurred first (up to approximately 5 years)
Secondary	Overall Survival, as Assessed Using RECIST Version 1.1		Baseline up to death/study completion (up to approximately 5 years)
Secondary	Phase II: Plasma Concentration of GDC-0032		Predose (0-4 hr) on Day 1, 15 Cycle 1 and Day 1 of Cycles 2, 6. Additionally 4 hr postdose on Day 15 Cycle 1 (Cycle length: 28 days)