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A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology
(DESTINY-PanTumor01)

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

Inoguchi Akihiro

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Not Recruiting

July. 01, 2021

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- 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

- 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.

Both

Advanced Solid Tumors With HER2

Drug: Trastuzumab deruxtecan 5.4 mg/kg via IV infusion on Day 1 of each cycle, every 3 weeks(q3w).

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.

- 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.

+81-3-3542-2511

May. 28, 2021

Yes

Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Supporting Materials: Study Protocol Statistical Analysis Plan (SAP) Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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