A Single Arm, Phase 2 Study of Datopotamab Deruxtecan, Carboplatin, and Pembrolizumab for Treatment-naive Brain Metastases From NSCLC (Non-small Cell Lung Cancer)

NCT06822543 | Recruiting Phase 2

• 1 other identifier: LACOG 0823
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II, single-arm, multicenter trial for patients with metastatic non-small cell lung cancer who have brain metastases and no known actionable mutations. Eligible patients will receive a combination of Datopotamab-deruxtecan, Carboplatin, and Pembrolizumab every three weeks for four cycles, followed by maintenance therapy with Datopotamab-deruxtecan and Pembrolizumab until disease progression or intolerable toxicity. Patients with intracranial progression but no systemic progression may receive stereotactic radiosurgery and continue treatment based on the investigator's decision.

Conditions

Lung Cancer; Non Small Cell Lung Cancer; Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Confirmed Intracranial Objective Response Rate (iORR) as Measured by the RANO-BM Criteria

  The intracranial objective response rate (iORR) is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to the RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria, as assessed by central review. The best overall CNS (central nervous system) response is determined based on a composite assessment of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status.

  Through study primary completion, an average of 2 years

Study Arms (1)

Single arm: pembrolizumab, datopotamab-deruxtecan, and carboplatin

EXPERIMENTAL

Study treatment: * INDUCTION: Pembrolizumab 200 mg IV Q3W; Datopotamab-Deruxtecan 6mg/kg IV Q3W; Carboplatin AUC 5 IV Q3W. * For four (4) cycles. * MAINTENANCE: Pembrolizumab 200 mg IV Q3W for 35 cycles; Datopotamab-Deruxtecan 6mg/ kg IV Q3W.\* * until disease progression or unacceptable toxicity.

Drug: Pembrolizumab; Drug: Datopotamab deruxtecan; Drug: Carboplatin

Interventions

Pembrolizumab DRUG

Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2).

Single arm: pembrolizumab, datopotamab-deruxtecan, and carboplatin

Datopotamab deruxtecan DRUG

Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload and a cleavable linker.

Single arm: pembrolizumab, datopotamab-deruxtecan, and carboplatin

Carboplatin DRUG

Carboplatin is a platinum compound chemotherapy used to treat lung cancer with a known safety profile. For more details on specific indications refer to the approved product label.

Single arm: pembrolizumab, datopotamab-deruxtecan, and carboplatin

Eligibility Criteria

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

You may qualify if:

• \- Male/female participants who are at least 18 years of age on the day of signing informed consent with a histologically confirmed diagnosis of NSCLC will be enrolled in this study.
• Histologically confirmed metastatic non-squamous NSCLC with PD-L1 tumor proportion score \<50% determined by local or central laboratory using antibodies 22C3'
• Documented negative test results for EGFR and ALK actionable genomic alterations by local test;
• No known actionable genomic alterations in ROS1, NTRK, RET, HER2, or MET.
• No prior systemic therapy for advanced or metastatic NSCLC. Patients who received chemotherapy or immunotherapy for localized or locally advanced NSCLC are eligible if progression occurred at least 6 months after the last dose of systemic treatment.
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1, including the following:
• Presence of 1 or more measurable central nervous system (CNS) metastases that have not received prior radiation therapy, or presence of 1 or more measurable central nervous system (CNS) metastases that has received prior radiation therapy but has unequivocally progressed within the radiation therapy field; Measurable brain metastasis is defined as any lesion that can be accurately measured in at least one dimension as ≥ 10mm. Patients with brain metastases lesions ≥ 5 mm and \< 10 mm are considered to have measurable disease and are allowed to be enrolled if MRI slice thickness is 1.5 mm or less.
• Presence of 1 or more measurable extracranial lesion; Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• \- No neurological symptoms that require immediate and significant intervention, in the opinion of the treating physician. Patients with neurologic symptoms that do not require significant medical intervention are allowed. Patients may also be enrolled after control of neurological symptoms that require immediate and significant intervention.
• Patients with neurologic symptoms that are controlled with anticonvulsants are allowed.
• Patients with neurologic symptoms that are controlled with stable (for at least 1 week), low dose dexamethasone (≤4 mg daily) are allowed.
• No leptomeningeal carcinomatosis.
• Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slide (preferably a minimum of 20 slides).

You may not qualify if:

• Has received prior radiotherapy to the brain within 2 weeks of the start of therapy, or received radiotherapy to the chest within 4 weeks of start of therapy, or that have ongoing radiation-related toxicities requiring corticosteroid.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Use of dexamethasone ≤ 4 mg/day (or another steroid at equivalent doses) is allowed for treatment of neurological symptoms.
• Has spinal cord compression.
• Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, which have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
• Has severe hypersensitivity (≥Grade 3) to either pembrolizumab and/or any of its excipients and/or Dato-DXd including its excipients (e.g. polysorbate 80).
• Has a history of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses (including pulmonary embolism within 3 months of enrollment, severe asthma, severe oxygen-dependent chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion) or autoimmune disease with lung involvement (i.e. rheumatoid arthritis, Sjogren disease, sarcoidosis, etc) with pulmonary involvement documented or suspected at screening.
• Clinically significant known corneal disease.
• Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• Severe infection within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
• Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1).
• Has not adequately recovered from major surgery or has ongoing surgical complications.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead
• Merck Sharp & Dohme LLC: collaborator
• AstraZeneca: collaborator

Study Sites (1)

FUNFARME - Hospital de Base de São José do Rio Preto

São José do Rio Preto, São Paulo, 15.090-000, Brazil

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

pembrolizumab; Carboplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• William Nassib William Junior

  Latin American Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager

CONTACT

+55 51 3384 5334; lacog0823@lacog.group

Laura Voelcker

CONTACT

+55 51 3384 5334; laura.voelcker@lacog.group

Study Design

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

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 12, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

BR (1)