Phase 2 Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer with Actionable Genomic Alterations

Phase 1

Active, not recruiting

• Conditions: Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-002774-27-FR
• Lead Sponsor: Daiichi Sankyo, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-30
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Subjects must meet all of the following criteria to be eligible for enrollment into the study:
1. Sign and date the ICF prior to the start of any study- specific qualification procedures.
2. Adults =18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements).
3. Has pathologically documented NSCLC that:
a. Is stage IIIB or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
b. Has one or more of the following documented activating tumor genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping or RET.
4. Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
5. Subject must meet at least the following for advanced or metastatic NSCLC:
a. Has progressed on or after at least one kinase inhibitor
b. Has progressed on or after at least one regimen of platinum-based chemotherapy
6. Willing and able to undergo a mandatory pre-treatment tumor biopsy for the measurement of TROP2 expression levels, confirmation of genomic alteration status and evaluation of other biomarkers. Biopsies may be collected from a lesion that has been irradiated provided that it can be documented that the lesion has increased/appeared since radiation
occurred, and that the biopsy is collected at least 3 months after radiation. If available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the biopsy collected during screening. Results from this biopsy will not be used to determine eligibility for the study. Screening biopsy should only be collected after all other eligibility criteria are met.
7. Archival tumor tissue from initial diagnosis is required, to the extent that archival tumor tissue is available.
8. Has measurable disease based on local imaging assessment using RECIST v1.1.
9. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.
10. Within 7 days before Cycle 1 Day 1, has adequate bone marrow function defined as:
a. Platelet count =100,000/mm3 (platelet transfusion is not allowed within 1 week prior to screening assessment).
b. Hemoglobin =9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
c. Absolute neutrophil count =1500/mm3 (granulocyte-colony stimulating factor administration is not allowed within 1 week prior to screening assessment).
11. Within 7 days before Cycle 1 Day 1, has:
- Adequate hepatic function, defined as:
? Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =2.5 × upper limit of normal (ULN) or AST/ALT =5.0 x ULN if transferase elevation is due to liver metastases).
? Total bilirubin (TBL) =1.5 × ULN or <3.0 mg/dL in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinemia).
OR
- Mild or moderate impaired hepatic function in a maximum of 12 subjects defined as:
? Mild hepatic dysfunction (a maximum of 6 subjects): TBL >ULN to =1.5 × ULN or AST >ULN.
? Moderate hepatic dysfunction (a maximum of 6 subjects): TBL >1.5 × ULN and =3 × ULN and any AST.
After a maximum of 12 subjects with mild or moderate hepatic dysfunction have been enrolled, subsequent subjects with mild or moderate hepatic dys

Exclusion Criteria

Subjects who meet any of the following criteria will be disqualified from entering the study:
1. 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 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
Note: A CT or magnetic resonance imaging (MRI) scan of the brain at baseline is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator should consider delay of study treatment to document stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of all screening activity may be required).
2. Has leptomeningeal carcinomatosis.
3. Prior treatment with:
a. An ADC containing a chemotherapeutic agent targeting topoisomerase I.
b. TROP2-targeted therapy.
4. Uncontrolled or significant cardiovascular disease, including:
a. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >470 milliseconds (msec) for females or >450 msec for males (based on the average of screening triplicate 12-lead ECG determinations).
b. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.
c. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
d. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to class I CHF and have LVEF =50% (by either an ECHO or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible.
e. History of serious cardiac arrhythmia requiring treatment.
f. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan. within 28 days before Cycle 1 Day 1.
g. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1.
5. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
6. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
7. Clinically significant corneal disease.
8. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Note: Subjects with localized fungal infections of skin or nails are eligible.
9. Has known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ counts/levels >250,

Study & Design

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