Clinical trial NCT06686394: Study of Patritumab Deruxtecan With Other Anticancer Agents in Participants With HER2 Positive Breast Cancer That Has Spread and Cannot Be Surgically Removed (MK-1022-009)
Official title: HERTHENA-Breast-01: A Phase 1b/2, Multicenter, Open-label, Dose-Finding Study to Evaluate the Safety and Antitumor Activity of Patritumab Deruxtecan in Participants With HER2 Positive Unresectable Locally Advanced Breast Cancer or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Neoplasms
Breast Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2024-11-13
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain breast cancers. The breast cancers being studied are HER2 positive unresectable locally advanced or metastatic (the cancer has spread to other parts of the body). The goals of this study are to learn:

* About the safety and how well people tolerate of patritumab deruxtecan
* How many people have the cancer respond (get smaller or go away) to treatment

Detailed description: The following countries will be participating in the trial: Canada, United Kingdom, Israel, Japan, South Korea, and USA.

Eligibility criteria: Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has histologically confirmed HER2+ locally advanced unresectable breast cancer or metastatic breast cancer
* Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load before allocation
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 7 days before start of study intervention

Arm 1:

* Has received at least a minimum of 2 and a maximum of 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
* Had disease progression on or after any previous trastuzumab deruxtecan (T-DXd) treatment

Arm 2:

-Has received no more than 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting

Arm 3:

-Has received and had disease progression from T-DXd treatment in any setting and a maximum of 3 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting. T-DXd must be the most recent therapy received before enrollment.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Uncontrolled or significant cardiovascular disease
* History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/interstitial lung disease
* Has clinically severe respiratory compromise
* Has any history of or evidence of any current leptomeningeal disease
* Has clinically significant corneal disease
* Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection
* HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Evidence of spinal cord compression or brain metastases
* Has an active infection requiring systemic therapy
* Concurrent active HBV and HCV infection
* Has had major surgical procedure (excluding placement of vascular access) less than 28 days

Arm 3 ONLY

- Has received prior treatment with tucatinib, lapatinib, or neratinib, or any investigational HER2-targeted tyrosine kinase inhibitors in the locally advanced or metastatic setting

Primary outcomes:
measure: Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
timeFrame: Up to 21 days
measure: Number of Participants with One or More Adverse Events (AEs)
timeFrame: Up to approximately 13 months
measure: Number of Participants who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Patritumab Deruxtecan Antibody-Drug Conjugate (ADC)
timeFrame: At designated time points (up to ~24 months)
measure: Trough Concentration (Ctrough) of Patritumab Deruxtecan ADC
timeFrame: At designated time points (up to ~24 months)
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Patritumab Deruxtecan ADC
timeFrame: At designated time points (up to ~24 months)
measure: Maximum Plasma Concentration (Cmax) of Total Patritumab Deruxtecan Antidrug Antibody (ADA)
timeFrame: At designated time points (up to ~24 months)
measure: Trough Concentration (Ctrough) of Total Patritumab Deruxtecan ADA
timeFrame: At designated time points (up to ~24 months)
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Total Patritumab Deruxtecan ADA
timeFrame: At designated time points (up to ~24 months)
measure: Maximum Plasma Concentration (Cmax) of Patritumab Deruxtecan Free Payload
timeFrame: At designated time points (up to ~24 months)
measure: Trough Concentration (Ctrough) of Patritumab Deruxtecan Free Payload
timeFrame: At designated time points (up to ~24 months)
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Patritumab Deruxtecan Free Payload
timeFrame: At designated time points (up to ~24 months)
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0052)
state: New Jersey
city: Greenville
country: United States
facility: Prisma Health - Upstate (ITOR)_Edenfield ( Site 0053)
state: South Carolina
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0011)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0012)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0010)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0030)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: