A clinical trial to evaluate the efficacy and safety of Trastuzumab Deruxtecan in treating patients with HER2 positive Solid Tumors

Phase 2

Recruiting

• Conditions: Neoplasm of unspecified behavior of unspecified site,

• Registration Number: CTRI/2021/03/031930
• Lead Sponsor: AstraZeneca AB

Brief Summary

This is an open-label, multi-center, multi-cohort, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment in locally advanced unresectable metastatic patients with HER2-overexpressed (IHC 3+ or IHC 2+) and HER2 low (IHC 1+) selected solid tumors not eligible for curative therapy. This study will consist of 7 cohorts of urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors. Patients will be enrolled at approximately 120 sites globally.

 All patients must be ≥ 18 years of age (other age restrictions may apply as per local regulations), RECIST v1.1 evaluable, and WHO/ECOG performance status of 0 to 1 at enrolment. Patients previously treated with prior HER2-targeting therapy will be eligible for the study.

 Tumor evaluation using RECIST v1.1 will be conducted at screening (within 28 days before first dose of study drug) and every 6 weeks (± 1 week) relative to the date of first dose of IP until RECIST v1.1 Investigator assessed objective disease progression, withdrawal of consent, or death by any cause. Regardless of whether study drug is discontinued or delayed, patients will be evaluated until disease progression assessed by RECIST v1.1, as per the study schedule, and then followed for OS until the end of the study, unless the patient withdraws consent to participate in the study.

 Treatment in this study with T-DXd will continue until any discontinuation criteria are met, including symptomatic deterioration, radiological progression, or Investigator determination that the patient is no longer benefiting from study treatment

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-16
• Last Update Posted: 2024-07-16

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

• Informed consent 1.
• Capable of giving signed informed consent 2.
• Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the AstraZeneca Genomic Initiative 3.
• Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, or analyses.
• Male and female patients must be at least 18 years of age at the time of signing the ICF.
• Type of patient and disease characteristics 5.
• Locally advanced, unresectable, or metastatic disease based on most recent imaging.
• Patients with locally advanced unresectable metastatic solid tumors with histology specific to respective cohorts, who have progressed following at least one prior systemic treatment for metastatic or advanced disease, or who have no satisfactory alternative treatment option.
• The respective cohorts for patient inclusion are: •Cohort 1: Biliary tract cancer •Cohort 2: Bladder cancer •Cohort 3: Cervical cancer •Cohort 4: Endometrial cancer •Cohort 5: Ovarian cancer •Cohort 6: Pancreatic cancer •Cohort 7: Rare tumors 6.
• Patients must have HER2-overexpression (IHC 3+ or IHC 2+) 7.
• All patients must provide an existing FFPE tumor sample for tissue-based IHC staining to centrally determine HER2-expression and other correlatives.
• Has an Eastern Cooperative Oncology Group Performance status (ECOG PS) of 0 1.
• Adequate organ and bone marrow function within 14 days before treatment assignment 12.
• Has adequate treatment washout period before randomisation/enrolment, 13.
• Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner.
• Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 7 months after the last dose of IP.
• Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to at least 4 months after the final dose of IP.
• Female patients must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.

Exclusion Criteria

• 1.Known somatic DNA mutation of HER2 (ERBB2) without tumoral HER2-expression as defined in inclusion criteria 6.
• 2.Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or NSCLC.
• 3.Uncontrolled intercurrent illness, including but not limited to ongoing or active infection, uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
• 4.Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
• Patients with clinically inactive brain metastases may be included in the study 5.Patients with a medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event, unstable angina pectoris, and stroke.
• 6.Has a corrected QT interval by Fridericias formula (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG 7.History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• 8.Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder, and prior pneumonectomy.
• 9.Has a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
• 10.Uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
• 11.Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
• 12.Patients receiving treatment with chloroquine or hydroxychloroquine are not allowed to participate in the study, unless there is a washout period of at least 14 days prior to the first dose of study treatment.
• 13.Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.
• 14.Has a concomitant medical condition that would increase the risk of toxicity in the opinion of the Investigator.
• 15.Known allergy or hypersensitivity to the IP or any of the study drug excipients.
• 17.Multiple primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other curatively treated solid tumors.
• 18.Pregnant or breastfeeding female patients.
• 19.Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd. 20.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and staff at the study site).
• 21.Judgment by the Investigator that the patient should not participate in the study, if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• 22.Previous treatment assignment in the present study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2-expressing tumor types	Confirmed ORR according to RECIST v1.1, as assessed by Investigator | Timepoint is every 6 weeks (± 1 week relative to date of first dose of IP) until RECIST v1.1 Investigator assessed objective disease progression

Secondary Outcome Measures

Name	Time	Method
To assess the safety and tolerability of T-DXd:	•Assessed by the occurrence of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, electrocardiogram, and ECHO or MUGA results
To further evaluate the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2-expressing tumor types:	Investigator assessments, based on RECIST v1.1
•Proportion of patients alive and progression-free at 6 months and 12 months	To further investigate the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2-expressing tumor types as measured by OS

Trial Locations

Locations (7)

Artemis Hospital; 🇮🇳 Gurgaon, HARYANA, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute; 🇮🇳 Mumbai, MAHARASHTRA, India

Meenakshi Mission Hospital and Research Institute; 🇮🇳 Madurai, TAMIL NADU, India

Rajiv Gandhi Cancer Institute and Research Centre; 🇮🇳 Delhi, DELHI, India

Tata Medical Center, Kolkata; 🇮🇳 Kolkata, WEST BENGAL, India

Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Artemis Hospital

🇮🇳Gurgaon, HARYANA, India

Dr Hari Goyal

Principal investigator

harig@artemishospitals.com