DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer
- 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
- EUCTR2020-004643-80-BE
- Lead Sponsor
- Daiichi Sankyo, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 590
1. Has the ability to provide written informed consent by signing and dating the ICF prior to the start of any study-specific qualification procedures
2. Adults =18 years
3. Has a life expectancy =3 months based on Investigator’s opinion.
4. Has pathologically documented Stage IIIB, IIIC, or Stage IV NSCLC with or without actionable genomic alteration(s) (AGA) at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition) and meets the following criteria for NSCLC:
a. Subjects Without AGA:
- Subjects must have documented negative test results for EGFR and ALK genomic alterations. If test results for EGFR and ALK are not available, subjects are required to undergo testing performed locally for these genomic alterations.
- Subjects have no known genomic alterations in ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
- Subjects with known KRAS mutations (testing during screening is not mandatory), in the absence of any driver genomic alterations, are eligible and must meet the prior therapy requirements for subjects without actionable genomic alterations described below. These subjects must be stratified as NSCLC without AGA at the time of randomization.
b. Subjects With AGA:
- Subjects must have 1 or more documented actionable genomic alteration: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
5. Subjects must have documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC
6. Subject must meet the following prior therapy requirements:
Subjects without AGA must meet ONE of the following prior therapy requirements for advanced or metastatic NSCLC:
a. Received platinum-based chemotherapy in combination with a-PD-1/a-PD-L1 monoclonal antibody as the only prior line of therapy
OR
b. Received platinum-based chemotherapy and a-PD-1/a-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy
Subjects with AGA must meet the following prior therapy requirements for advanced or metastatic NSCLC:
a. Has been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the subject’s genomic alteration at the time of screening; OR one or more of the agents specified in the protocol
b. Has received platinum-based chemotherapy as the only prior line of cytotoxic therapy
c. May have received up to one a-PD-1/a-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
7. Must undergo a pre-treatment tumor biopsy procedure
OR
If available, tumor tissue previously retrieved from a biopsy procedure performed within 2 years prior to the subject signing informed consent 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 pre-treatment biopsy procedure during Screening. If a documented law or regulation prohibits (or does not approve) sample collection, then such samples will not be collected/submitted.
Note: Results from the TROP2 testing of the pre-treatment tumor biopsy will not be used to determine eligibility for the study.
9. Has measurable disease based on local imaging assessment using RECIST v1.1
10. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or1 at Screening
11. Within 7 days before randomization, has adequate bone marrow function as detailed in the study protocol
12. Within 7 days before randomization, h
1. Has mixed small-cell lung cancer and NSCLC histology
2. Has spinal cord compression or clinically active central nervous system (CNS) 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. Please see additional details in the protocol
3. Has leptomeningeal carcinomatosis or metastasis
4. Had prior treatment with:
a. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
b. TROP2-targeted therapy
c. Docetaxel
5. Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently meeting the prior therapy requirements for Stage III or metastatic NSCLC disease as described in Inclusion Criterion 6
6. Has NSCLC disease that is eligible for definitive local therapy alone
7. Uncontrolled or significant cardiac disease as described in detail in the protocol
8. 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
9. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement, or prior pneumonectomy
10. Has significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage
11. Clinically significant corneal disease
12. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections
13. Has known human immunodeficiency virus (HIV) infection that is not well controlled
14. Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen [HBsAg], anti-hepatitis B surface antibody [anti-HBs], anti-hepatitis B core antibody [anti-HBc], or hepatitis B virus [HBV] DNA), and/or hepatitis C infection (as per hepatitis C virus [HCV] RNA) within 28 days of randomization. See section 5.2 of protocol for details.
15. Has a history of malignancy, other than NSCLC except a) adequately resected non melanoma skin cancer, b) curatively treated in situ disease, or c) other solid tumors curatively treated, with no evidence of disease for =3 years.
16. Concomitant medical condition that would increase the risk of toxicity in the opinion of the Investigator
17. Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade =1 or baseline
18. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or docetaxel
19. History of severe hypersensitivity reactions to other monoclonal antibodies
20. Is pregnant or breastfeeding or planning to become pregnant
For the full list of exclusion criteria, please see protocol section 5.2.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of DS-1062a with that of docetaxel, as measured by PFS and OS, for subjects with NSCLC with or without actionable genomic alterations;Secondary Objective: - To further evaluate the efficacy of DS-1062a compared with docetaxel<br>- To further evaluate the safety of DS-1062a compared with docetaxel<br>- To assess the PK of DS-1062a<br>- To assess the immunogenicity of DS-1062a;Primary end point(s): - PFS assessed by BIRC: defined as the time from randomization to the earlier of the dates of the first radiographic disease progression or death due to any cause. <br>- OS: defined as the time from randomization to death due to any cause.;Timepoint(s) of evaluation of this end point: At the pre-determined timepoints as described in the protocol.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - PFS assessed by the investigator<br>- ORR<br>- DoR<br>- TTR<br>- DCR<br>- EORTC-QLQLC13 (except questions 36 and 37)<br>- TEAEs and other safety parameters during the study<br>- PK<br>- Immunogenicity;Timepoint(s) of evaluation of this end point: At the pre-determined timepoints as described in the protocol.