Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer
Status and phase
Completed
Phase 1
Conditions
Breast Cancer
Urothelial Carcinoma
Treatments
Drug: Nivolumab
Drug: Trastuzumab deruxtecan
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
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.
Full description
The purpose of this phase 1b (Part 1, Part 2) study is to assess the combination of a test drug (trastuzumab deruxtecan) with nivolumab in participants with HER2-expressing breast and urothelial cancer who had disease progression during or after prior therapies, did not respond to standard therapies, or for whom no standard therapy is available.
The study will be performed in 2 parts.
- Part 1 is to test different doses of trastuzumab deruxtecan when given along with a fixed dose of nivolumab, and establish the maximum tolerated dose/recommended dose for expansion, when used in combination with nivolumab
- Part 2 is to assess the efficacy and safety of this dose combination.
Enrollment
86 patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
Inclusion criteria
- Is the age of majority (adulthood) in their country
- Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
- Has pathologically documented breast cancer or urothelial cancer that is unresectable or metastatic, and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit, and as specified in each study cohort
- Has an adequate archival tumor sample available for the central laboratory to determine eligibility to participate
- Has at least 1 measurable lesion per RECIST version 1.1
- Has cardiac, bone marrow, kidney, liver, blood and clotting test results required per protocol
- Has had an adequate washout period before enrollment since previous surgery and other treatment
- If reproduction is possible, agrees to use protocol-defined methods of contraception (or completely abstain from heterosexual intercourse) from screening to at least 7 months for females and males after the last dose of study drug
- Agrees to avoid harvesting sperm or ova for any reason from screening to at least 7 months for females and males after the last dose of study drug
- Has a life expectancy of at least 3 months
Exclusion criteria
- Has received prior treatment with nivolumab or trastuzumab deruxtecan
- Has medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association classes II-IV). Troponin levels above upper limit of normal (ULN) at screening (as defined by the manufacturer) and without any MI-related symptoms should have a cardiologic consultation before enrollment to rule out MI.
- Has a corrected QT interval by Fredericia (QTcF) prolongation to > 470 ms (females) or > 450 ms (males) based on an average of the screening triplicate 12-lead electrocardiogram
- Has history of non-infectious interstitial lung disease (ILD/pneumonitis) (that required steroids), has ILD/pneumonitis currently, or it cannot be ruled out by imaging at screening
- Has a condition (other than active autoimmune disease) that requires systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of starting study treatment
- Is pregnant or breastfeeding, or planning to become pregnant
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Sequential Assignment
Masking
None (Open label)
86 participants in 6 patient groups
Dose Escalation (3.2 mg/kg)
Experimental group
Description:
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.
Treatment:
Drug: Trastuzumab deruxtecan
Drug: Nivolumab
Dose Escalation (5.4 mg/kg)
Experimental group
Description:
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.
Treatment:
Drug: Trastuzumab deruxtecan
Drug: Nivolumab
Dose Expansion - Cohort 1
Experimental group
Description:
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.
Treatment:
Drug: Trastuzumab deruxtecan
Drug: Nivolumab
Dose Expansion - Cohort 2
Experimental group
Description:
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.
Treatment:
Drug: Trastuzumab deruxtecan
Drug: Nivolumab
Dose Expansion - Cohort 3
Experimental group
Description:
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.
Treatment:
Drug: Trastuzumab deruxtecan
Drug: Nivolumab
Dose Expansion - Cohort 4
Experimental group
Description:
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.
Treatment:
Drug: Trastuzumab deruxtecan
Drug: Nivolumab
Trial contacts and locations
29
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Data sourced from clinicaltrials.gov
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