Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer

Conditions

• Breast Cancer
• Urothelial Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Trastuzumab deruxtecan — DRUG
  The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
• Nivolumab — DRUG
  Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.

Study Details

This is a study of trastuzumab deruxtecan for the treatment of HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based regimens. Participants will receive this study drug along with a cancer drug, an immune checkpoint inhibitor, anti-PD1, called nivolumab. The study will be done in two parts: * Part 1 is to identify the recommended dose to use for treatment. * Part 2 is to find out how well the combination works, and how safe and tolerable it is.

Key Dates

Start date

Aug 2, 2018

Status verified

Dec 2024

Primary completion

Jul 22, 2021

Completion

Sep 12, 2023

Study Design

Enrollment

86 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Dose Escalation (3.2 mg/kg)
  Participants with HER2-expressing breast cancer who received starting intravenous dose of trastuzumab deruxtecan at 3.2 mg/kg and a fixed intravenous dose of 360mg of nivolumab every 3 weeks (Q3W). Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab was administered on Day 1 of each 21-day cycle. The DLT observation period will be the first 2 cycles.
• Experimental: Dose Escalation (5.4 mg/kg)
  Participants with HER2-expressing breast cancer who received starting intravenous dose of trastuzumab deruxtecan at 3.2 mg/kg and a fixed intravenous dose of 360mg of nivolumab every 3 weeks (Q3W). Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab was administered on Day 1 of each 21-day cycle. The DLT observation period will be the first 2 cycles.
• Experimental: Dose Expansion - Cohort 1
  Cohort 1: Participants with pathologically documented advanced/metastatic breast cancer that has centrally-determined positive HER2 expression (IHC 3+ or IHC 2+/ISH+) \[as defined by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines\]. These participants received prior ado-trastuzumab emtansine (T-DM1). Participants will receive the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
• Experimental: Dose Expansion - Cohort 2
  Cohort 2: Participants with pathologically documented advanced/metastatic breast cancer that has centrally-determined low HER2 expression (IHC 1+ or IHC 2+/ISH-), who have exhausted treatments that can confer any clinically meaningful benefit (eg, other therapies such as hormonal therapy for patients who are hormone receptor positive). Participants received the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
• Experimental: Dose Expansion - Cohort 3
  Cohort 3: Participants with pathologically documented advanced/metastatic urothelial carcinoma that has centrally-determined HER2 expression of IHC 2+ or 3+, who received prior platinum-based therapy with documented progression. Participants received the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
• Experimental: Dose Expansion - Cohort 4
  Cohort 4: Participants with pathologically documented advanced/metastatic urothelial carcinoma that has centrally-determined HER2 expression of IHC 1+, who received prior platinum-based therapy with documented progression. Participants received the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.

Primary Outcome Measure

Number of Participants With Dose-Limiting Toxicities at 3.2 mg/kg and 5.4 mg/kg Dose Level in Participants With HER2-expressing Advanced Breast Cancer in Dose Escalation [ Time Frame: Cycles 1 and 2 (each cycle is 21 days) ]

Locations (10)

Find similar trials in Santa Monica, CA

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