A Phase 2, Multicenter, Open-Label, 2-Cohort Study of Trastuzumab Deruxtecan (DS-8201a), an Anti-HER2 Antibody Drug Conjugate (ADC), for HER2-Over-Expressing or -Mutated, Unresectable and/or Metastatic Non Small Cell Lung Cancer (NSCLC)

Phase 1

• Conditions: HER2-over-expressing or -mutated, unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC); MedDRA version: 21.1Level: LLTClassification code 10001246Term: Adenosquamous cell lung cancer NOSSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10001255Term: Adenosquamous cell lung cancer stage unspecifiedSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10001253Term: Adenosquamous cell lung cancer stage IIIBSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10001252Term: Adenosquamous cell lung cancer stage IIIASystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004781-94-NL
• Lead Sponsor: DAIICHI SANKYO, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-07
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 181

Inclusion Criteria

Inclusion Criteria:
1. Must have provided informed consent for study participation (see Section 15.3) before performance of any study-specific procedure or test.
2. Age =20 y old in Japan, =18 y old in other countries.
3. Pathologically documented unresectable and/or metastatic nonsquamous NSCLC.
4. Has relapsed from or is refractory to standard treatment or for which no standard treatment is available.
5. For Cohort 1 and Cohort 1a only: HER2-overexpression (IHC 2+ or 3+) status must be assessed and confirmed by Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory or equivalent, from an archival tumor tissue sample.
For Cohort 2 only: Documented any known activating HER2 mutation from an archival tumor tissue sample analyzed by CLIA laboratory or equivalent, specifically exon 20 insYVMA (Y772_A775dup), insGSP
(G778_P780dup), insTGT (G776delinsVC), single base pair substitutions L755S, V777L, or S310F or another HER2 mutation listed in the appendix (see Section 17.7). Note: HER2 mutation documented only from a liquid biopsy sample cannot be used for enrollment.
6. Presence of at least 1 measurable lesion assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
7. Is willing and able to provide an adequate archival tumor tissue sample. Fine needle aspirates are not acceptable
8. Is willing to undergo a tissue biopsy, after the completion of the most recent treatment regimen.
9. Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 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 153
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion Criteria

Exclusion Criteria:
1. Previously treated with HER2-targeted therapies, except for pan-HER class tyrosine kinase inhibitors.
2. For Cohort 1 and Cohort 1a only: Has known HER2 mutation.
3. Uncontrolled or significant cardiovascular disease, including any of the following:
a. Medical history of myocardial infarction within 6 months prior to enrollment
b. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) 28 d prior to enrollment
c. Troponin levels consistent with myocardial infarction (as defined by the manufacturer) 28 d prior to enrollment
d. History of unstable angina, or serious cardiac arrhythmia requiring treatment
e. Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to enrollment
f. Has a corrected QT interval (QTcF) prolongation to > 470 ms (females) or >450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG).
4. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
5. Has clinically significant corneal disease in the opinion of the Investigator.
6. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated
symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with
corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 wk must have elapsed between the end of whole brain radiotherapy
and study enrollment.
7. Has multiple primary malignancies within 3 y, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.

Study & Design

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