A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations

JRCT ID: jRCT2031210132

Registered date:04/06/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced Solid Tumors With HER2
• Date of first enrollment: 30/08/2021
• Target sample size: 100
• Countries of recruitment: Belgium,Japan,Canada,Japan,South Korea,Japan,Spain,Japan,United States,Japan,Italy,Japan,France,Japan,Denmark,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

Confirmed objective response rate by RECIST 1.1 based on independent central review (ICR). [ Time Frame: An average of approximately 12 months. ]
Confirmed ORR per RECIST 1.1 is the proportion of patients with Complete Response or Partial Response that is subsequently confirmed, based on ICR.

Secondary Outcome

- Duration of response (DoR) based on ICR and Investigator assessment. [ Time Frame: An average of approximately 12 months. ]
- DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on ICR and Investigator assessment.
- Disease control rate (DCR) based on ICR and Investigator assessment. [ Time Frame: An average of approximately 12 months. ]
- DCR is the proportion of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on ICR and Investigator assessment.
- Progression free survival (PFS) based on ICR and Investigator assessment. [ Time Frame: An average of approximately 12 months. ]
- PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on ICR and Investigator assessment.
- Proportion of patients alive and progression-free. [ Time Frame: At 6 and 12 months. ]
- Proportion of patients who are alive and progression-free based on ICR and Investigator assessment.
- Confirmed Objective Response Rate (ORR) based on investigator assessment. [ Time Frame: An average of approximately 12 months. ]
- Confirmed ORR per RECIST 1.1 is the proportion of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment
- Overall survival (OS). [ Time Frame: An average of approximately 20 months. ]
- OS is the time form the date of first dose of study treatment until death due to any cause.
- Occurrence of adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: An average of approximately 14 months. ]
- Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
- Serum concentration of T-DXd. [ Time Frame: An average of approximately 14 months. ]
- Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
- Serum concentration of total anti-HER2 antibody. [ Time Frame: An average of approximately 14 months. ]
- Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
- Serum concentration of MAAA-1181a. [ Time Frame: An average of approximately 14 months. ]
- Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for MAAA-1181a.
- The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd. [ Time Frame: An avarage of approximately 14 months. ]
- Individual participant data and descriptive statistics will be provided for data at each time point.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 120age old
• Gender: Both

Include 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 (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772_A775dup / A775_G776insYVMA, L755S, G778_P780dup / P780_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) ) on tumor tissue, 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
- All patients have measurable target disease assessed by the Investigator based on RECIST v1.1

Exclude criteria

- HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
- HER2 mutant NSCLC.
- Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke.
- History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening.
- Corrected QT interval by Fridericia's formula (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG.
- 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.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04639219