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-PL
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-11
• Last Update Posted: 14 June 2021

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

• History of non-infectious pneumonitis/ILD that required steroids,
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 gastroesophageal
junction, or non-small cell lung cancer
• Medical conditions that may interfere with the subject's participation
in the study.

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.