Phase 2 Study of HER3-DXd in Locally Advanced or Metastatic Solid Tumors

Phase 1

Recruiting

Conditions: ocally Advanced or Metastatic Solid Tumors
MedDRA version: 21.1Level: LLTClassification code: 10065252Term: Solid tumor Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-507641-29-00

Lead Sponsor: Daiichi Sankyo Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

Sign and date the ICF, prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement., If male, the subject must be surgically sterile or willing to use highly effective birth control upon enrollment, during the Treatment Period, and for =4 months following the last dose of study drug., Male subjects must not freeze or donate sperm starting at screening and throughout the study period and =4 months after the final study drug administration., Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions., Sub study: Participant is taking part in the Phase II open-label study., Sub study: Participant provides consent to participate in the interview sub-study via the Study Informed Consent Form (ICF)., Sub study: Participant consents to be audio recorded., Sub study: Participant resides in Belgium, Spain, Japan, Korea, Taiwan, continental US (Puerto Rico is excluded), UK and Australia., Sub study: Participant can communicate and read fluently in country local language including Belgian-French, Spanish, Japanese, Korean, Taiwanese-Mandarin or English., Sub study: Participant is physically able to participate in a one-on-one, approximately 45-minute telephone interview (conducted in one sitting) using an internet-enabled computer or other device (such as a tablet) with screensharing / screen-viewing capabilities, Is a male or female subject aged =18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old, Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) (see details on page 55), Has =1 measurable lesion on computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST v1.1 by investigator assessment., Provides a pretreatment tumor tissue sample of sufficient quantity (see details on page 56), Has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at screening, Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day (see table on page 57), If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control upon enrolment, during the Treatment Period, and for 7 months following the last dose of study drug (see table on page 57)., Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study Treatment Period and for =7 months after the final study drug administration.

Exclusion Criteria

Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations), Had inadequate washout period prior to Cycle 1 Day 1 (see details on page 58), Had prior treatment with an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan)., Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved by the National Cancer Institute – Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) to Grade =1 or baseline (see details on page 59)., Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following: a. Adequately treated nonmelanoma skin cancer b. Adequately treated intraepithelial carcinoma of the cervix c. Any other curatively treated in situ disease., Has uncontrolled or significant cardiovascular disorder prior to Cycle 1 Day 1 (see details on page 59), Has active HCV infection (see details on page 60), Has uncontrolled HIV1/2 infection (see details on page 60), Has active or uncontrolled HBV infection (see details on page 60), Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active serious infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the investigator’s opinion, make it high risk for the subject to participate in the study or that would jeopardize compliance with the protocol., Has known hypersensitivity to either the drug substance or inactive ingredients in the drug product., Has nasopharyngeal cancer, Is a female subject who is pregnant or breastfeeding or intends to become pregnant during the study, Has prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator’s opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results, Sub study: Participant is unable to adhere to the requirements of the interview sub-study, Has mucosal or uveal melanoma, Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening, Has clinically severe respiratory compromise (based on the investigator’s assessment) resulting from intercurrent pulmonary illnesses (see details on page 58), Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study, Has any history of or evidence of current leptomeningeal disease, Has clinically significant corneal disease, Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic or untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and not requiring treatment with c

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of HER3-DXd monotherapy for each indicated locally advanced or metastatic tumor;Secondary Objective: To assess the safety and tolerability of HER3-DXd monotherapy for each indicated locally advanced or metastatic tumor, To further assess the efficacy of HER3 DXd monotherapy for each indicated locally advanced or metastatic tumor, To evaluate the PK of HER3-DXd monotherapy for each indicated locally advanced or metastatic tumor, To evaluate HER3 protein expression in tumor tissue and its relationship with HER3-DXd efficacy;Primary end point(s): The primary endpoint of the study is ORR as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):TEAEs and other safety parameters during the study;Secondary end point(s):Duration of response (DoR);Secondary end point(s):Clinical benefit rate (CBR);Secondary end point(s):Disease control rate (DCR);Secondary end point(s):Time to response (TTR);Secondary end point(s):Progression-free survival (PFS) evaluated by the investigator per RECIST v1.1;Secondary end point(s):Overall survival (OS);Secondary end point(s):PK endpoints;Secondary end point(s):Correlation between HER3 protein expression at baseline (as determined by HER3 IHC assay) and efficacy

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