The study of Trastuzumab Deruxtecan to assess its efficacy, safety and tolerability in Patients with Selected HER2 Expressing Tumors

Phase 1

• Conditions: Treatment in locally advanced unresectable metastatic patients with HER2 overexpressed (IHC 3+ or IHC 2+) and HER2 low (1+) selected solid tumors not eligible for curative therapy.; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-001574-29-IT
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-24
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

• Locally advanced, unresectable, or metastatic disease based on most recent imaging.
• 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: Epithelial ovarian cancer
-Cohort 6: Pancreatic cancer
-Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.
• Progressed following prior treatment or who have no satisfactory alternative treatment option.
• Prior HER2 targeting therapy is permitted.
• HER2 expression for eligibility may be based on local or central assessment.
• Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
• Has protocol- defined adequate organ function including cardiac, renal and hepatic function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

•Uncontrolled intercurrent illness
•History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
•Lung-specific intercurrent clinically significant severe illnesses
• Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
•Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART
•Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.
•Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer.

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 T-DXd in patients with metastatic or unresectable tumors in selected HER2 expressing tumor types.;Secondary Objective: -To further assess the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2-expressing tumor types<br>-To assess the safety and tolerability of T-DXd<br>-To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181 in serum<br>-To investigate the immunogenicity of T-DXd;Primary end point(s): Objective Response Rate (ORR).;Timepoint(s) of evaluation of this end point: An average of approximately 12 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Duration of response (DoR).<br>2)Disease control rate (DCR).<br>3)Progression free survival (PFS).<br>4)Proportion of patients alive and progression-free at 6 months and 12 months.<br>5)Overall survival (OS).<br>6)Proportion of patients alive at 6 months and 12 months.<br>7)Occurrence of adverse events (AEs) and serious adverse events (SAEs).<br>8)Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181.<br>9)The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd.;Timepoint(s) of evaluation of this end point: 1) An average of approximately 18 months.<br>2) An average of approximately 18 months.<br>3) An average of approximately 18 months.<br>4) Up to 12 months.<br>5) An average of approximately 30 months.<br>6) Up to 12 months.<br>7) An average of approximately 24 months.<br>8) An average of approximately 24 months.<br>9) An average of approximately 24 months.