A Phase II Study of T-DXd in Patients with Selected HER2-expressing Tumors

JRCT ID: jRCT2051240075

Registered date:26/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HER2 Expressing Solid Tumors
• Date of first enrollment: 22/07/2024
• Target sample size: 200
• Countries of recruitment: Australia,Japan,Belgium,Japan,Canada,Japan,Czechia,Japan,India,Japan,Italy,Japan,Korea,Japan,Netherlands,Japan,Poland,Japan,Russia,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional
• Intervention(s): Drug: Trastuzumab deruxtecan 5.4 mg/kg via IV infusion on Day 1 of each cycle, every 3 weeks(q3w).

Outcome(s)

Primary Outcome

- Objective Response Rate (ORR)
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Secondary Outcome

- Duration of response (DoR)
DOR is defined as the time from the date of first documented response until the date of documented progression or death.
- Disease control rate (DCR)
DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
- Progression free survival (PFS)
PFS is the time from date of first dose of study treatment until the date of objective disease progression or death.
- Proportion of patients alive and progression-free at 6 months and 12 months
The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates).
- Overall survival (OS)
OS is the time from date of first dose of study treatment until death due to any cause.
- Proportion of patients alive at 6 and 12 months
The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
- Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
- Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
- The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd
Individual participant data and descriptive statistics will be provided for data at each time point.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 120age old
• Gender: Both

Include criteria

- Locally advanced, unresectable, or metastatic disease based on most recent imaging.

The respective cohorts for patient inclusion are:
- Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
- Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
- Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+.
- Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.
- Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.

- Progressed following prior treatment or who have no satisfactory alternative treatment option.
- Prior HER2 targeting therapy is permitted.
- HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 for gastric cancer.
- IHC and ISH results by central assessment as pre-defined for each cohort

- 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.

Exclude 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.
- Patients with primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.
- Medical conditions that may interfere with the subject's participation in the study.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04482309