DATOPOTAMAB DERUXTECAN for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Has the ability to provide written informed consent by signing and dating the ICF prior to the start of any study-specific qualification procedures\n- Within 7 days before randomization, has adequate hepatic function as detailed in the study protocol\n- Within 7 days before randomization, has adequate renal function, including mild or moderate renal function, as detailed in the study protocol\n- Has left ventricular ejection fraction (LVEF) ≥50% by either ECHO or MUGA scan within 28 days before randomization\n- Has adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × ULN\n- Has an adequate treatment washout period before randomization, as defined in the study protocol\n- Adults ≥18 years\n- Has a life expectancy ≥3 months based on Investigator's opinion.\n- Subjects must have documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC\n- 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.\n- 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.\n- Has measurable disease based on local imaging assessment using RECIST v1.1\n- Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or1 at Screening\n- Within 7 days before randomization, has adequate bone marrow function as detailed in the study protocol"}

Exclusion criteria

• {"criterion_text":"- Has mixed small-cell lung cancer and NSCLC histology\n- Has significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage\n- Clinically significant corneal disease\n- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections\n- Has known human immunodeficiency virus (HIV) infection that is not well controlled\n- 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.\n- 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.\n- Concomitant medical condition that would increase the risk of toxicity in the opinion of the Investigator\n- Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline\n- 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\n- History of severe hypersensitivity reactions to other monoclonal antibodies\n- 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\n- Is pregnant or breastfeeding or planning to become pregnant\n- Has leptomeningeal carcinomatosis or metastasis\n- Had prior treatment with: a. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I b. TROP2-targeted therapy c. Docetaxel\n- 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\n- Has NSCLC disease that is eligible for definitive local therapy alone\n- Uncontrolled or significant cardiac disease as described in detail in the protocol\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS measured as time from randomization to first radiographic progression or death (per text: 'time from randomization to the earlier of the dates of the first radiographic disease progression or death due to any cause')."}
• {"endpoint_text":"- OS is defined as the time from randomization to death due to any cause.","definition_or_measurement_approach":"OS measured as time from randomization to death from any cause."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Same definition/measurement as primary PFS (time from randomization to first radiographic progression or death)."}
• {"endpoint_text":"- ORR is defined as the proportion of subjects who achieved a BOR of CR or PR.","definition_or_measurement_approach":"ORR measured as proportion achieving best overall response (BOR) of complete response (CR) or partial response (PR)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"DoR measured from first documentation of objective response (CR or PR) to first radiographic progression or death."}
• {"endpoint_text":"- DCR is defined as the proportion of subjects who achieved a BOR of CR, PR, or SD.","definition_or_measurement_approach":"DCR measured as proportion achieving BOR of CR, PR, or stable disease (SD)."}
• {"endpoint_text":"- TTR is defined as the time from randomization to the date of the first documentation of objective response (CR or PR) in responding subjects.","definition_or_measurement_approach":"TTR measured as time from randomization to first documentation of objective response (CR or PR) among responders."}

Belgium

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

07-10-2025

Processing Time Days

459

Number Of Sites

2

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

458

Number Of Sites

2

Number Of Participants

21

Spain

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

458

Number Of Sites

7

Number Of Participants

88

Netherlands

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

05-11-2025

Processing Time Days

488

Number Of Sites

1

Number Of Participants

19

Poland

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

458

Number Of Sites

8

Number Of Participants

16

Germany

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

07-10-2025

Processing Time Days

459

Number Of Sites

3

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

528

Number Of Sites

7

Number Of Participants

97

Primary sponsor

Full Name

Daiichi Sankyo Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pharmaceutical Product Development LLC

Responsibilities

ADA testing; code 4

Name

Bioclinica Inc.

Responsibilities

Central imaging

Name

Bioclinica Inc.

Responsibilities

ECG

Name

Syneos Health Netherlands B.V.

Responsibilities

Multiple operational roles (codes: 1,10,11,12,13,2,5,6,8) as listed in sponsor duties

Name

Q Squared Solutions Limited

Responsibilities

Sample shipment, SARS-CoV-2 Real Time PCR

Name

Almac Clinical Services LLC

Responsibilities

code 3

Third parties

• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"ADA testing; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Snapiot Inc.","duties_or_roles":"code 7","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"codes: 1,10,11,12,13,2,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"ECG","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Sample shipment, SARS-CoV-2 Real Time PCR","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}