DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Apr 2021 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc

External identifiers

EU CT number

2023-509865-19-00

EudraCT number

2020-004643-80

ClinicalTrials.gov

NCT04656652

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Efficacy, Pharmacodynamic, Pharmacokinetic, Safety, Others, Pharmacogenomic, Therapy

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 objectives 4

1. To further evaluate the efficacy of DS-1062a compared with docetaxel
2. To further evaluate the safety of DS-1062a compared with docetaxel
3. To assess the PK of DS-1062a
4. To assess the immunogenicity of DS-1062a

Conditions and MedDRA coding

Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

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. Subjects must have documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC
5. 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 α-PD- 1/α-PD-L1 monoclonal antibody as the only prior line of therapy OR b. Received platinum-based chemotherapy and α-PD-1/α-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 α-PD-1/α-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
6. 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 pretreatment 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.
7. Has measurable disease based on local imaging assessment using RECIST v1.1
8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or1 at Screening
9. Within 7 days before randomization, has adequate bone marrow function as detailed in the study protocol
10. Within 7 days before randomization, has adequate hepatic function as detailed in the study protocol
11. Within 7 days before randomization, has adequate renal function, including mild or moderate renal function, as detailed in the study protocol
12. Has left ventricular ejection fraction (LVEF) ≥50% by either ECHO or MUGA scan within 28 days before randomization
13. Has adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × ULN
14. Has an adequate treatment washout period before randomization, as defined in the study protocol

Exclusion criteria 20

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PFS is defined as the time from randomization to the earlier of the dates of the first radiographic disease progression or death due to any cause.
2. OS is defined as the time from randomization to death due to any cause.

Secondary endpoints 5

1. PFS is defined as the time from randomization to the earlier of the dates of the first radiographic disease progression or death due to any cause.
2. ORR is defined as the proportion of subjects who achieved a BOR of CR or PR.
3. DoR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first.
4. DCR is defined as the proportion of subjects who achieved a BOR of CR, PR, or SD.
5. TTR is defined as the time from randomization to the date of the first documentation of objective response (CR or PR) in responding subjects.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 7

Locations

7 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications