A study of Trastuzumab Deruxtecan to assess its safety, tolerability, immune response, and inhibition of tumor activity when given alone or in combination with other agents in patients with HER2 OverexpressingGastric Cancer

Phase 1

• Conditions: Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing gastric cancer; 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: EUCTR2019-004483-22-IT
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-21
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1 Male and female participants must be at least 18 years of age
2 Disease Characteristics:
Locally advanced, unresectable, or metastatic disease
Pathologically documented adenocarcinoma of the stomach or GEJ with HER2 overexpression (IHC 3+ or ICH 2+/ISH+)
3. For Part 1, progression on or after at least one prior trastuzumab-containing regimen
For Part 2, previously untreated for unresectable or metastatic adenocarcinoma of the stomach or GEJ with HER2 overexpression.
4. Has measurable target disease assessed by the Investigator based on RECIST version 1.1
5. 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 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion Criteria

1. History of active primary immunodeficiency, known HIV, active HBV or HCV infection, or active tuberculosis.
2. Uncontrolled intercurrent illness
3. History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
4. Lung-specific intercurrent clinically significant severe illnesses
5. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
6. Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Part 1:<br>To evaluate the safety of T-DXd in combination with durvalumab and/or chemotherapy in participants with HER2-overexpressing, locally<br>advanced, unresectable or metastatic gastric cancer.<br><br>Part 2:<br>To assess the antitumor activity of T-DXd combinations at the RP2D from Part 1;Secondary Objective: 1. Part1: To assess the preliminary antitumor activity of T-DXd combinations<br>2. Part 2: To assess the safety and tolerability of T-DXd monotherapy and T-DXd combination regimens<br>3. To assess the PK of T-DXd, total anti-HER2 antibody, MAAA-1181, and durvalumab in all arms<br>4. To investigate the immunogenicity of T-DXd;Primary end point(s): Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs)<br>Part 2: Confirmed Objective Response Rate (ORR);Timepoint(s) of evaluation of this end point: Part 1: Safety will be assessed for approximately 24 months from informed consent.<br>Part 2: At an average of approximately 12 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Part 1: Confirmed Objective Response Rate (ORR)<br>Part 2: Occurrence of adverse events (AEs) and serious adverse events (SAEs)<br>Parts 1 and 2: Disease Control Rate (DCR); Duration of Response (DoR); Progression-free survival (PFS); Overall Survival (OS); Serum concentration of T-DXd; Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms; Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab; Presence of ADAs for T-DXd and durvalumab (in study arms including T-DXd and durvalumab);Timepoint(s) of evaluation of this end point: Part 1 only: At an average of approximately 12 months.<br>Part 2 only: Safety will be assessed for approximately 24 months from informed consent.<br>Parts 1 and 2: At an average of approximately 18 months.