A Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer

Sponsor
Hoffmann-La Roche
Study ID
NCT04298918
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Placebo — DRUG
    Participants will receive oral placebo in combination with trastuzumab emtansine.
  • Venetoclax — DRUG
    Participants will receive oral venetoclax.
  • Trastuzumab emtansine — DRUG
    Participants will receive intravenous (IV) trastuzumab emtansine.

Study Details

This two-part study is composed of two stages: a Phase Ib stage consisting of a dose-escalation phase and an expansion phase; and a Phase II, randomized, placebo-controlled, double-blind, multicenter stage. The Phase Ib stage will assess the safety and tolerability, determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D), and evaluate the preliminary efficacy of trastuzumab emtansine in combination with venetoclax in participants with previously treated human epidermal growth factor receptor 2 (HER2) positive unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). Additional patients may be enrolled in an expansion phase to evaluate the safety, tolerability, and efficacy of trastuzumab emtansine in combination with venetoclax at RP2D in patients with previously treated HER2-positive LABC or MBC who have previously received either trastuzumab emtansine or trastuzumab deruxtecan (DS-8201a). The Phase II randomized stage will evaluate the safety, efficacy, tolerability, and pharmacokinetics of trastuzumab emtansine in combination with venetoclax at RP2D compared with trastuzumab emtansine plus placebo in participants with previously treated HER2-positive LABC or MBC who have not received prior trastuzumab emtansine therapy, either alone or in combination with other anti-cancer therapies.

Key Dates

Start date
Sep 23, 2020
Status verified
Oct 2021
Primary completion
Feb 4, 2021
Completion
Feb 4, 2021

Study Design

Enrollment
1 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Escalation Phase
    Participants received venetoclax in combination with a fixed dose of trastuzumab emtansine.
  • Experimental: Dose Expansion Phase
    Participants were to receive venetoclax at the Phase II Recommended Dose (RP2D) in combination with trastuzumab emtansine.
  • Experimental: Randomized Phase II Arm 1
    Participants were to receive trastuzumab emtansine + placebo.
  • Experimental: Randomized Phase II Arm 2
    Participants were to receive trastuzumab emtansine + venetoclax.

Primary Outcome Measure

Dose Escalation: Number of Participants With Adverse Events [ Time Frame: Baseline up until 28 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 20 weeks). ]

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