Substudy 01I: A Study of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I/KEYMAKER-U01I)

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• The main inclusion criteria include but are not limited to the following:
• Histologically or cytologically confirmed diagnosis of Stage IV squamous non-small cell lung cancer (NSCLC)
• Has documented disease progression per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1), as assessed by investigator after receiving an anti-programmed cell death protein 1 (anti-PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy for Stage IV disease
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
• Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

You cannot join if

• The main exclusion criteria include but are not limited to the following:
• Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
• Has uncontrolled or significant cardiovascular disorder
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), or prior pneumonectomy
• Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
• Has clinically significant corneal disease
• Has previously received docetaxel as monotherapy or in combination with other therapies
• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
• Evidence of any leptomeningeal disease
• Has one or more of the following indicators of interstitial lung disease (ILD)/pneumonitis: any history of ILD/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), current diagnosis of ILD, clinical or radiographic suspicion of ILD
• Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
• Active infection requiring systemic therapy
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
• Known history of, or active, neurologic paraneoplastic syndrome
• History of allogeneic tissue/solid organ transplant
• Has not adequately recovered from major surgery or have ongoing surgical complications

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

raludotatug deruxtecan. An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody against the tumor-associated antigen (TAA) cadherin-6 (CDH6; CDH-6) conjugated to deruxtecan, which is comprised of an enzymatically cleavable tetrapeptide-based linker and MAAA-1181a (DXd), the cytotoxic DNA topoisomerase I inhibitor derivative of exatecan, with potential antineoplastic activity. Upon administration of raludotatug deruxtecan, raludotatug targets and binds to CDH6-expressing tumor cells. Upon cellular uptake and lysosomal degradation of the linker, DXd targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication and apoptosis. This inhibits the proliferation of CDH6-expressing tumor cells. CDH6, a member of the cadherin family and overexpressed by a variety of cancers, plays a key role in tumor cell proliferation. NCI Drug Dictionary

ifinatamab deruxtecan. An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) conjugated, via an enzymatically cleavable tetrapeptide-based linker, to the cytotoxic DNA topoisomerase I inhibitor and exatecan (DX-8951) derivative DXd (MAAA-1181a; MAAA-1181), with potential antineoplastic activity. Upon administration of the anti-B7-H3/DXd ADC DS-7300a, the anti-B7-H3 antibody targets and binds to B7-H3-expressing tumor cells. Upon cellular uptake and lysosomal degradation of the linker, DXd targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication and apoptosis. This inhibits the proliferation of B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It plays a key role in tumor growth and immune responses. The ADC allows for reduced systemic exposure and enhanced delivery of the cytotoxic agent DXd. NCI Drug Dictionary

Treatments listed in the registry

• R-DXD (Biological): IV Infusion
• I-DXD (Biological): IV Infusion
• Docetaxel (Drug): IV Infusion
• Rescue Medications (Drug): Participants receive rescue medications consisting of a combination regimen to include corticosteroids with a 5-hydroxytryptamine subtype 3 receptor antagonist and/or a neurokinin-1 receptor antagonist, all per approved product label and following institutional standards or local guidelines.
• Rescue Medication (Drug): Participants are premedicated with corticosteroids per approved product label and following institutional standards or local guidelines.

Randomized · Parallel · masking: Single

Main goals

• Objective Response Rate (ORR) (Up to approximately 81 months)
• Number of participants who experience one or more adverse events (AEs) (Up to approximately 81 months)
• Number of participants who discontinue study intervention due to an AE (Up to approximately 81 months)

Other goals

• Duration of Response (DOR)
• Progression-free Survival (PFS)
• Overall Survival (OS)

Planned enrollment: 144 (estimated).

• University of Kentucky Chandler Medical Center ( Site 0019), Lexington, Kentucky
• MedStar Franklin Square Medical Center ( Site 0033), Baltimore, Maryland
• Texas Oncology - DFW ( Site 8003), Dallas, Texas
• Virginia Cancer Specialists (VCS) ( Site 0408), Fairfax, Virginia

42 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06780098
• NCI Drug Dictionary: C179214
• NCI Drug Dictionary: C171577

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 6, 2026. Public record; not medical advice.