About the study

This study intends to define the recommended Phase 2 dose of ifinatamab deruxtecan (I-DXd) based on the efficacy, safety, and pharmacokinetics (PK) results observed in participants with Extensive-stage Small Cell Lung Cancer (ES-SCLC) who received at least 1 prior line of platinum-based chemotherapy and a maximum 3 prior lines of therapy and to investigate I-DXd anti-tumor activity in this population.

Who can take part?

You may be eligible to participate in the study if you meet the following criteria:

Inclusion criteria

Participants must meet all the following criteria to be eligible for enrollment into the study:

1. Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
2. Participant must have at least one lesion, not previously irradiated, amenable to core biopsy.
3. Male or female subjects aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
4. Histologically or cytologically documented ES-SCLC.
5. At least one measurable lesion according to RECIST v1.1 as assessed by the investigator.
6. Prior therapy with at least one platinum-based line as systemic therapy for extensive-stage disease with at least two cycles of therapy (except in the case of early objective PD).
7. Documentation of radiological disease progression on or after most recent systemic therapy.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

Exclusion criteria

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents.
2. Prior treatment with an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan).
3. Clinically active brain metastases, spinal cord compression or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
4. Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or arterial thromboembolic event.
5. Clinically significant corneal disease.
6. Uncontrolled or significant cardiovascular disease.
7. History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
8. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses,
9. Chronic steroid treatment (maximum dose of 10 mg daily prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD) or topical steroids (for mild skin conditions) or intra-articular steroid injections.
10. History of malignancy other than SCLC within the 3 years prior to enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal (GI) tract tumors and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
11. History of allogeneic bone marrow, stem cell, or solid organ transplant.
12. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute
13. Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0), Grade ≤1 or baseline.
14. History of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
15. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection (including HIV infection).
16. Active or uncontrolled hepatitis B or C infection.
17. Active, known, or suspected autoimmune disease.
18. Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, substance abuse).
19. Has received a live vaccine within 30 days prior to the first dose of study drug.
20. Female who is pregnant or breast-feeding or intends to become pregnant during the study.
21. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant.

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

Study locations

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How to apply

Determine if a study site for this clinical trial is near you. Contact the study to apply.