Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)

Study Overview
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Brief Summary
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This phase II MATCH treatment trial identifies the effects of GDC-0032 (taselisib) in patients whose cancer has a genetic change called PIK3CA mutation. Taselisib may stop the growth of cancer cells by blocking PIK3CA, a protein that may be needed for cell growth. Researchers hope to learn if taselisib will shrink this type of cancer or stop its growth.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: Patients receive taselisib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Official Title
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MATCH Treatment Subprotocol I: GDC-0032 (Taselisib) in Patients With Tumors (Other Than Breast Cancer) With PIK3CA Mutation But Without KRAS Mutation or PTEN Loss

Conditions
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Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Taselisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol Patients must have a PIK3CA mutation as determined via the MATCH Master Protocol Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) Patients with known left ventricular dysfunction must have echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible Patients must have a fasting glucose =< 125 mg/dL NOTE: Please provide clear documentation that the glucose test was conducted at a fasting state Patients with prior treatment with an mTOR inhibitor are acceptable. These include, but are not limited to: temsirolimus, everolimus, ridaforolimus, sirolimus, CC-223, MLN128 (INK128), DS-3078, CC-115, AZD-2014, AZD8055 Exclusion Criteria: Patients must not have known hypersensitivity to GDC-0032 (taselisib) or compounds of similar chemical or biologic composition Patients must not have breast cancer Patients with squamous cell carcinoma of the lung who have PIK3CA mutations who have access to AND are eligible for Lung-MAP (S1400) are not eligible Patients must not have KRAS mutations, and/or PTEN mutation or loss, detected in the tumor sample as determined by the MATCH screening assessment. PTEN loss will be determined by immunohistochemistry Patients must not have had prior therapy with a PI3K inhibitor or PI3K/mTOR inhibitor. These include, but are not limited to: BEZ235, XL-765 (SAR245409), GDC-0980, PF-04691502, PF-05212384 (PKI-587), SF-1126, GSK 2126458, P-7170, BGT-226, LY3023414, GDC-0084, DS-7423, BKM-120 (buparlisib), PX-866, XL-147, GDC-0941 (pictilisib), VS-5584, BAY-80-6946, ZSTK-474, WX 037, AZD8835, GSK2636771, GS-9820, BYL719, MLN1117 (INK1117), idelalisib, TGR1202, RP6530, duvelisib (IPI-145), CUDC-907. Prior GDC-0032 (taselisib) is not allowed Patients must not have had prior therapy with an Akt inhibitor. These include, but are not limited to: MK-2206, GSK690693, AZD5363, triciribine, perifosine, GSK2141795, GSK2110183, SR13668, BAY1125976, GDC-0068 (ipatasertib), LY2780301, ARQ092 Patients must not have type 1 or 2 diabetes requiring anti-hyperglycemic medication (e.g. metformin, glipizide, insulin) Patients must not have current dyspnea at rest or require any daily supplemental oxygen Patients must not have history of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g. diverticulitis)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (taselisib)<br>Patients receive taselisib 4 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Taselisib<br>* Given PO<br>* Other names: RO5537381;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR. | Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-Month Progression-free Survival (PFS) Rate | PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. | Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS is determined | 
| Progression-free Survival (PFS) | PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. | Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration |