Phase 3 Randomized Trial of Datopotamab Deruxtecan Versus Docetaxel in Advanced or Metastatic Non-Small Cell Lung Cancer with or without Genomic Alterations

Trial ID: 2023-509865-19-00
Protocol: DS1062-A-U301
Sponsor: Daiichi Sankyo Inc.

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Non-small cell lung cancer

Objectives

The primary objective of this Phase 3 randomized study is to compare the **efficacy** of DS-1062a with that of docetaxel in subjects with advanced or metastatic **non-small cell lung cancer** (NSCLC), with or without actionable genomic alterations. This is measured by progression-free survival (PFS) and overall survival (OS), which are critical endpoints in assessing the clinical benefit of cancer therapies.

Secondary objectives include:

Further evaluation of the efficacy of DS-1062a compared with docetaxel.
Further evaluation of the safety of DS-1062a compared with docetaxel.
Assessment of the pharmacokinetics (PK) of DS-1062a.
Assessment of the immunogenicity of DS-1062a.

Participants

The clinical trial involves a total of **418 participants** diagnosed with **Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)**. The study population includes both male and female adults aged 18 years and older. Participants were selected based on their ability to provide informed consent and meet specific health criteria, including adequate hepatic, renal, and bone marrow function, as well as a left ventricular ejection fraction of at least 50%. The trial includes individuals with a life expectancy of at least three months and those who have documented radiographic disease progression following prior treatment regimens. Participants may have received previous therapies, including platinum-based chemotherapy and monoclonal antibodies, depending on the presence of actionable genomic alterations. The study population is characterized by a diverse range of health statuses, with an Eastern Cooperative Oncology Group performance status of 0 or 1. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial also includes vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across different demographic groups.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of DS-1062a compared to **docetaxel** in patients with advanced or metastatic **non-small cell lung cancer** (NSCLC). The trial aims to assess progression-free survival (PFS) and overall survival (OS) as primary endpoints. The study is expected to span approximately 4.5 years, with an estimated recruitment start date of December 28, 2020, and an anticipated end date of July 28, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as adequate hepatic and renal function, measurable disease, and prior treatment history. Following randomization, participants will receive either DS-1062a or docetaxel via **intravenous** infusion. The treatment period is set for a maximum of 72 weeks, with regular follow-up visits to monitor safety, efficacy, and any adverse events. These visits will include assessments such as imaging studies to evaluate disease progression and laboratory tests to ensure continued eligibility.

The end-of-study visit will occur after the completion of the treatment period or upon early termination. Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The expected length of participant involvement is contingent upon individual response to treatment and overall health status, with a minimum life expectancy of three months required for inclusion. The trial's design ensures rigorous monitoring and data collection to support the evaluation of the investigational product's therapeutic potential in the specified patient population.

Treatment

The clinical trial involves the administration of two primary treatments: **Docetaxel** and **Datopotamab deruxtecan**. **Docetaxel** is utilized as a comparator treatment in this study. It is a **concentrate for solution for infusion** and is administered intravenously. The dosage is calculated based on body surface area, with a maximum daily and total dose of 75 mg/m². The treatment period for **Docetaxel** is set at a maximum of 72 weeks. The active substance, **Docetaxel**, is of chemical origin and is not formulated for pediatric use.

**Datopotamab deruxtecan**, identified by the sponsor product code DS-1062a, serves as the experimental medication in this trial. It is provided as a **solution for infusion** and is also administered intravenously. The dosage is determined by body weight, with a maximum daily and total dose of 6.0 mg/kg. Similar to **Docetaxel**, the treatment period for **Datopotamab deruxtecan** is capped at 72 weeks. The active substance, **Datopotamab deruxtecan**, is a protein of other origin, and the formulation is not intended for pediatric use. The product is developed by DAIICHI SANKYO, INC.

Efficacy

The efficacy of the investigational product DS-1062a compared to **docetaxel** will be assessed in a Phase 3 randomized clinical trial involving subjects with advanced or metastatic non-small cell lung cancer (NSCLC), with or without actionable genomic alterations. The primary efficacy endpoints include Progression-Free Survival (PFS) and Overall Survival (OS). 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. OS is defined as the time from randomization to death due to any cause.

Secondary efficacy endpoints include Objective Response Rate (ORR), Duration of Response (DoR), Disease Control Rate (DCR), and Time to Response (TTR). ORR is defined as the proportion of subjects who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). DoR is the time from the first documentation of objective response (CR or PR) to the first radiographic disease progression or death. DCR is the proportion of subjects who achieved a BOR of CR, PR, or Stable Disease (SD). TTR is the time from randomization to the first documentation of objective response (CR or PR) in responding subjects.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

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

cancel

Exclusion Criteria

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

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	28 Dec 2020	12
France	Not Recruiting	28 Dec 2020	97
Germany	Not Recruiting	28 Dec 2020	8
Italy	Not Recruiting	28 Dec 2020	21
The Netherlands	Not Recruiting	28 Dec 2020	—
Poland	Not Recruiting	28 Dec 2020	16
Spain	Not Recruiting	28 Dec 2020	88
Netherlands	—	—	19