TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases

NCT04512261 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IIT2019-21-Basho-TOPAZ
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open label trial to assess the safety and efficacy of tucatinib in combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain metastases (BCBM). A total of 33 patients with untreated or previously treated and progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy will be enrolled. The study will determine the recommended dose of tucatinib in this combination and assess the efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM.

Conditions

Breast Cancer; Brain Metastases; HER2-positive Breast Cancer; CNS Disease

Keywords

tucatinib; pembrolizumab; trastuzumab

Outcome Measures

Primary Outcomes (2)

• 24-week CNS disease control rate (DCR)

  Percentage of patients who experience objective tumor response \[ partial response (PR) or complete response (CR) \] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain.

  24 weeks

• Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab

  24 weeks

Secondary Outcomes (5)

• CNS objective response rate (ORR)

  From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.

• Systemic ORR

  From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.

• Progression-free survival (PFS)

  From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.

• Overall Survival (OS)

  From baseline until death or 3 years, whichever occurs first.

• Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration

  From first dose of study treatment until 30 days after the last dose of study treatment.

Study Arms (1)

Tucatinib + Pembrolizumab + Trastuzumab

EXPERIMENTAL

Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.

Drug: Tucatinib; Drug: Pembrolizumab; Drug: Trastuzumab

Interventions

Tucatinib DRUG

Initial dosage of trial treatment for tucatinib will be given as 300 mg (dispensed as 2 x 150 mg tablets) orally twice a day for Days 1 - 21 of each 3-week cycle during the treatment period.

Also known as: Tukysa

Tucatinib + Pembrolizumab + Trastuzumab

Pembrolizumab DRUG

Initial dosage of trial treatment for pembrolizumab will be given as 200 mg by intravenous infusion every 3 weeks on Day 1 of each 3-week cycle during the treatment period. Pembrolizumab will be administered for a maximum of 35 doses.

Also known as: Keytruda

Tucatinib + Pembrolizumab + Trastuzumab

Trastuzumab DRUG

Initial dosage of trial treatment for trastuzumab will be given as 8 mg/kg by intravenous (IV) infusion once on Day 1 of Cycle 1, and 6 mg/kg by IV every 3 weeks on Day 1 of each 3-week cycle starting on Cycle 2 during the treatment period.

Also known as: Herceptin

Tucatinib + Pembrolizumab + Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• ECOG performance status of 0-2.
• HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.
• Untreated or previously treated and progressing CNS disease.
• Measurable CNS metastases.
• Must be able to undergo MRI of the brain.
• Adequate organ function.

You may not qualify if:

• Any indication for immediate CNS-directed therapy.
• History of generalized or complex partial seizures.
• Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases.
• Leptomeningeal disease.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
• Prior therapy with tucatinib.
• Active autoimmune disease that has required systemic treatment in excess of prednisone 10mg daily or equivalent in the past 2 years.

Sponsors & Collaborators

• Reva Basho: lead
• Merck Sharp & Dohme LLC: collaborator
• Seagen Inc.: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Central Nervous System Diseases

Interventions

tucatinib; pembrolizumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Reva Basho, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: August 13, 2020
• Study Start: June 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: July 1, 2022

Record last verified: 2022-06

Locations

US (1)