Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer

NCT04940325 | Active Not Recruiting Phase 2

• 2 other identifiers: 2023-505924-71-002020/3187
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 9

Brief Summary

This study aims to evaluate the efficacy and safety of DS-1062a in participants with metastatic, unresectable NSCLC having progressed on one, but not more than three previous standard therapies. Moreover, the immune effects, the predictors of resistance and response to treatment, the effect of the chemotherapy on deoxyribonucleic acid (DNA) replication will be assessed and will help identify the subgroups that will mostly benefit from the treatment. The pharmacokinetics of the product and the anti-drug antibody (ADA) will be also evaluated. A total of 100 participants are planned to be included in the study. Participants will receive, every three weeks, a dose of DS-1062a equivalent to 6 mg/kg of body weight until progression or until unacceptable toxicity. Tumor evaluation will be performed every six weeks by the mean of a computed tomography for the thorax, abdomen and pelvis (TAP CT-scan) or a magnetic resonance imaging (MRI). Brain and/or bone CT scans will be also performed throughout the study for participants with brain and/or bone metastasis. The safety of the product will be assessed, through complete clinical exams, biological tests, electrocardiograms (ECGs), cardiac echographies (ECHOs) and through the collection of ongoing toxicities or adverse events.

Conditions

Metastatic Lung Cancer; Advanced Non Small Cell Lung Cancer; Unresectable Non-small Lung Cancer

Keywords

Metastatic Lung Cancer; Advanced lung cancer; Antibody drug conjugate; ADC; Non small Cell lung Cancer; NSLC; Advanced non small Cell lung Cancer; Metastatic non small Cell lung Cancer; Datopotamab deruxtecan; Refractory NSCLC; Refractory Non small Cell lung Cancer; DS-1062; DS-1062a; unresectable lung cancer; unresectable non small Cell lung Cancer; Advanced NSCLC; Metastatic NSCLC; Unresectable NSCLC

Outcome Measures

Primary Outcomes (1)

• Evaluation of objective response rate (ORR) based on investigator assessment

  ORR is defined as the proportion of participants who achieved a confirmed complete response (CR) or partial response (PR) observed on treatment and assessed by investigators

  During treatment period, an average of 4 months

Secondary Outcomes (9)

• Evaluation of duration of response (DoR)

  From cycle 2 (Week 3) up to 3 years after the EoT, an average of 39 months]

• Evaluation of progression free Survival (PFS)

  From cycle 2 (Week 3) up to 3 years after the EoT, an average of 39 months]

• Evaluation of clinical benefit ratio (CBR)

  From cycle 2 (Week 3) up to 3 years after the EoT, an average of 39 months]

• To evaluate incidence of adverse events (AEs)

  During treatment (at each cycle), at EoT and up to 35 days after EoT, an average of 5 months]

• To evaluate proportion of treatment modification

  During treatment, an average of 4 months

Other Outcomes (2)

• To assess physical functioning sub-scale score of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) based on a scale from 1 to 4, where higher scores mean worse outcome

  During treatment (Cycles 1, 2, 3 and then every 2 cycles), at EoT and then up to 3 years after EoT, an average of 40 months]

• To assess global health sub-scale score of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) based on a scale from 1 to 7, where higher scores mean better outcome

  During treatment (Cycles 1, 2, 3 and then every 2 cycles), at EoT and up to 3 years after EoT, an average of 40 months]

Study Arms (1)

DS-1062a

EXPERIMENTAL

All patients included in the study will receive DS-1062a at a dose of 6 mg/kg every 3 weeks until progression or until unacceptable toxicity

Drug: DS-1062a

Interventions

DS-1062a DRUG

First infusion for 90 minutes and then infusion duration can be decreased to 30 minutes if participant didn't experience infusion related reactions (IRR)

DS-1062a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with histologically confirmed diagnosis of advanced and/or unresectable NSCLC
• Participants who received at least one line and not more than three lines of therapy and considered by the investigator as refractory to standard treatment or for which no standard treatment is available:
• Participants who have no known mutation or mutation without an approved targeted therapy: anti programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) containing therapy and a platinum-doublet regimen
• Participants who have known EGFR, BRAF, and MET mutation or ALK, ROS1, RET, NTRK fusion: one line of an approved targeted agent and one platinum-doublet regimen
• Metastatic site easily accessible to biopsy (with exception of bone metastasis)
• Presence of at least one measurable lesion (different from the biopsy site) according to RECIST v1.1
• ECOG status should be equal or less to one
• Life expectancy should be equal or more than 3 months
• Participants must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1
• Participants with asymptomatic and clinically stable treated brain metastasis, who require no treatment with corticosteroids and/or anticonvulsants. Participants must have a stable neurologic status for at least two weeks prior to Cycle 1 Day 1
• Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during the study and for at least 7 months after the last dose of study drug
• Contraceptive methods considered highly effective:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine device (IUD)

You may not qualify if:

• Participants unwilling to participate to the biological investigations and to perform biopsies and blood sample collection as required in the protocol
• Participants with only bone metastasis will be excluded, except if they have an accessible primary tumor which could be biopsied at baseline, on-treatment and end-of-treatment.
• Participant with any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.
• Participant with clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
• Any underlying pulmonary disorder
• Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement
• OR prior pneumonectomy
• Participants receiving chronic systemic corticosteroids at a dose higher than 10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study
• Participants with evidence of any leptomeningeal disease
• Participants with evidence of clinically active spinal cord compression or brain metastases
• Participants with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients (including but not limited to polysorbate 80) of DS-1062a
• Participants with a history of severe hypersensitivity reactions to other monoclonal antibodies
• Inadequate washout period prior to Cycle 1 Day 1, defined as:
• Whole brain radiation therapy within 14 days before treatment or stereotactic brain radiation therapy, within 7 days before treatment
• Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), within 14 days before treatment or 5 half-lives, whichever is longer

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• Daiichi Sankyo: collaborator

Study Sites (9)

Institut Bergonié

Bordeaux, 33076, France

Location

Institut de Cancérologie, CHRU Morvan de Brest

Brest, 29200, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Tenon

Paris, 75970, France

Location

Hospices Civils de Lyon - Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• David PLANCHARD, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One group of 100 patients treated with DS-102a

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 25, 2021
• Study Start: May 12, 2021
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

FR (9)