Phase Ib Dose-escalation Trial of Taselisib (GDC-0032) in Combination With Anti-HER2 Therapies in Participants With Advanced HER2+ Breast Cancer

NCT02390427 | Completed Phase 1 DMC

• 1 other identifier: 15-024
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is a way of gaining new knowledge about the combination of Taselisib with other drugs in the treatment of metastatic breast cancer. Taselisib is an investigational drug which works by blocking a protein called PI3K (phosphoinositide 3-kinase) that helps cancer cells grow. This drug has been used in laboratory experiments and information from these studies suggests that this drug may help to prevent or slow the growth of cancer cells. The main purpose of this study is to find the appropriate dose of Taselisib to be used with other drugs in further clinical studies. This is an open-label, 3+3 dose-escalation phase Ib study to identify the Maximum Tolerated Dose(s) (MTD) and to identify the recommended phase 2 dose (RP2D) of Taselisib. This study will be conducted in 4 separate arms. (A-D).

Conditions

Metastatic Breast Cancer; Recurrent Breast Cancer

Keywords

Metastatic Breast Cancer; Advanced Breast Cancer; Recurrent Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.

  28 Days

Secondary Outcomes (7)

• Clinical Benefit Rate (CBR) for efficacy of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.

  > or = 6 Months

• Progression Free Survival (PFS) for efficacy of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.

  2 Years

• Overall Survival for efficacy of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.

  2 Years

• Occurrence of AEs and SAEs during treatment with Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.

  2 Years

• Occurrence of dose delays or holds

  More than 7 Days

Study Arms (4)

Arm A

EXPERIMENTAL

Arm A \- Taselisib with Trastuzumab emtansine (also called T-DM1) * Taselisib administered orally, daily in each treatment cycle (3 weeks). * Trastuzumab emtansine (also called T-DM1) administered once via IV per treatment cycle (3 weeks).

Drug: Taselisib; Drug: Trastuzumab emtansine

Arm B

EXPERIMENTAL

Arm B -Taselisib with T-DM1 and Pertuzumab * Taselisib is administered oral, daily or every other day per treatment cycle (3 weeks). * Trastuzumab emtansine (also called T-DM1) administered once via IV per treatment cycle (3 weeks). * Pertuzumab- administered once via IV per treatment cycle (3 weeks).

Drug: Taselisib; Drug: Trastuzumab emtansine; Drug: Pertuzumab

Arm C

EXPERIMENTAL

Arm C: * Taselisib with Pertuzumab and Trastuzumab * Cohort C will not open without additional authorization from Genentech * Taselisib is administered oral, daily in each treatment cycle (3 weeks). * Trastuzumab administered once via IV per treatment cycle (3 weeks). * Pertuzumab- administered once via IV per treatment cycle (3 weeks).

Drug: Taselisib; Drug: Pertuzumab; Drug: Trastuzumab

Arm D

EXPERIMENTAL

Arm D * Taselisib with Pertuzumab, Trastuzumab, and Paclitaxel * Cohort will not be opened without additional authorization from Genentech * Taselisib- administered oral, daily in each treatment cycle (3 weeks). * Pertuzumab- administered once via IV per treatment cycle (3 weeks). * Trastuzumab administered once via IV per treatment cycle (3 weeks). * Paclitaxel- administered via IV, weekly for 3 weeks within each cycle.

Drug: Taselisib; Drug: Pertuzumab; Drug: Trastuzumab; Drug: Paclitaxel

Interventions

Taselisib DRUG

Also known as: GCD-0032

Arm A; Arm B; Arm C; Arm D

Trastuzumab emtansine DRUG

Also known as: T-DM1, Kadcyla

Arm A; Arm B

Pertuzumab DRUG

Also known as: Perjeta

Arm B; Arm C; Arm D

Trastuzumab DRUG

Also known as: Herceptin

Arm C; Arm D

Paclitaxel DRUG

Also known as: Taxol, Onxal

Arm D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic, locally advanced , or locally recurrent breast cancer
• Histologically confirmed HER2+ invasive breast cancer
• Measurable or non-measurable disease per RECIST v1.1
• Prior therapy - Prior trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1) are allowed. Patients who have received prior therapy with Taselisib (GDC-0032) or BYL-719 are excluded. There is no limit on the number of prior lines of therapy.
• ECOG performance status 0 or 1
• Normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3
• Platelets ≥100,000/mm3
• Total bilirubin \< 1.5 X institutional upper limit of normal. For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range
• AST (SGOT) and ALT (SGPT) \< 2.5 X institutional upper limit of normal
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min
• Fasting glucose ≤ 120 mg/dL and HbA1c \< 7%
• Left ventricular ejection fraction ≥ 50%
• Women of childbearing potential (including those who have had a tubal ligation) must have a documented negative pregnancy test within 14 days prior to planned initiation of Taselisib.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Anti-cancer therapy within 2 weeks prior to entering the study or those who have not recovered from acute adverse events due to agents administered more than 2 weeks earlier. Palliative radiation to bony metastases ≥2 weeks prior to study entry is allowed.
• Prior treatment with a PI3 kinase, AKT or mTOR inhibitor in which the patient experienced a Grade ≥3 drug related adverse event or otherwise would be at increased risk for additional PI3K related toxicity
• Currently receiving any other investigational agents. Treatment with an investigational agent within 2 weeks prior to planned initiation of study therapy is allowed provided that any drug related toxicity has completely resolved
• Major surgical procedure within 4 weeks prior to planned initiation of study therapy
• Significant traumatic injury within 3 weeks prior to planned initiation of study therapy
• Known untreated brain metastases are excluded. History of treated CNS metastases is okay, provided the following criteria are met:
• Disease outside the CNS is present.
• No evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
• No history of intracranial hemorrhage or spinal cord hemorrhage
• Not requiring anti-convulsants for symptomatic control
• Minimum of 3 weeks between completion of CNS radiotherapy and Cycle 1 Day 1 and recovery from significant (Grade ≥ 3) acute toxicity with no ongoing requirement for corticosteroid
• History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to the Taselisib drug formulation or other agents used in this study.
• Receiving any medications or substances that are inhibitors of CYP3A4.
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Active small or large intestine inflammation such as Crohn's disease or ulcerative colitis

Sponsors & Collaborators

• Otto Metzger, MD: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide; Ado-Trastuzumab Emtansine; pertuzumab; Trastuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Otto Metzger, MD

  Dana Farber Cancer Insitute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: April 20, 2015
• Primary Completion: December 1, 2022
• Study Completion: July 1, 2024
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (3)