A study to investigate anti-tumor activity and safety of trastuzumab deruxtecan in patients with solid tumors carrying specific HER2 mutations.

Phase 1

• Conditions: Treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology.; 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: EUCTR2020-002368-30-IT
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Adults =18 years old. Other age restrictions may apply as per local regulations.
• Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations locally determined by NGS, who have progressed following prior treatment or who have no satisfactory alternative treatment options.
• Prior HER2 targeted therapy is permitted.
• All patients must provide an FFPE tumor sample for retrospective central HER2 testing.
• LVEF =50%
• ECOG 0-1
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

• HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
• HER2 mutant NSCLC.
• History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening
• Lung-specific intercurrent clinically significant severe illnesses.
• History of active primary immunodeficiency, known HIV, active HBV or HCV infection
• 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).
• Has spinal cord compression or clinically active central nervous system metastases.

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 harboring specific HER2 activating mutations across tumor types.;Secondary Objective: - To further assess the efficacy of T-DXd in patients with metastatic or unresectable tumors harboring pre-specified HER2 activating mutations across 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-1181a in serum.<br>- To investigate the immunogenicity of T-DXd.;Primary end point(s): Confirmed objective response rate by RECIST v1.1 based on independent central review (ICR).;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) based on ICR assessment.<br>2) Disease control rate (DCR) based on ICR assessment.<br>3) Progression free survival (PFS) based on ICR assessment.<br>4) Confirmed Objective Response Rate (ORR) based on investigator assessment.<br>5) Overall survival (OS).<br>6) Occurrence of adverse events (AEs) and serious adverse events (SAEs).<br>7) Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181.<br>8) 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 12 months.<br>2) An average of approximately 12 months.<br>3) An average of approximately 12 months.<br>4) An average of approximately 12 months.<br>5) An average of approximately 20 months.<br>6) An average of approximately 14 months.<br>7) An average of approximately 14 months.<br>8) An average of approximately 14 months.