KEYMAKER-U01 Substudy 01I: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 144
- Locations
- 61
- Primary Endpoint
- Objective Response Rate (ORR)
Study Overview
Brief Summary
Researchers are looking for other ways to treat metastatic squamous non-small cell lung cancer (NSCLC). Squamous NSCLC is cancer that starts in squamous cells, which are flat cells that line the inside of the airways in the lungs. Metastatic means the cancer has spread to other parts of the body.
Standard treatment (usual treatment) for metastatic squamous NSCLC is immunotherapy with or without chemotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. However, standard treatment may not work or may stop working to treat metastatic squamous NSCLC.
Researchers want to learn if study treatments that are antibody drug conjugates (ADCs) can treat metastatic squamous NSCLC that did not respond (get smaller or go away) to standard treatment. An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells.
The main goals of this study are to learn about:
- The cancer response to the study treatments compared to chemotherapy
- The safety of the study treatments and if people tolerate them
This study is one of the substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
Detailed Description
The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Arm 2: Infinatamab deruxtecan (I-DXD) High Dose
Participants receive 12 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Intervention: I-DXD (Biological)
Arm 4: Docetaxel
Participants receive 75 mg/m^2 of Docetaxel, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Intervention: Docetaxel (Drug)
Arm 1: Raludotatug deruxtecan (R-DXD)
Participants receive 5.6 mg/kg of R-DXD, every 3 weeks (Q3W) (Day 1 of every 21-day cycle) via intravenous (IV) infusion until progressive disease (PD) or discontinuation.
Intervention: R-DXD (Biological)
Arm 2: Infinatamab deruxtecan (I-DXD) High Dose
Participants receive 12 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Intervention: Rescue Medications (Drug)
Arm 3: I-DXD Low Dose
Participants receive 8 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Intervention: I-DXD (Biological)
Arm 1: Raludotatug deruxtecan (R-DXD)
Participants receive 5.6 mg/kg of R-DXD, every 3 weeks (Q3W) (Day 1 of every 21-day cycle) via intravenous (IV) infusion until progressive disease (PD) or discontinuation.
Intervention: Rescue Medications (Drug)
Arm 3: I-DXD Low Dose
Participants receive 8 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Intervention: Rescue Medications (Drug)
Arm 4: Docetaxel
Participants receive 75 mg/m^2 of Docetaxel, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Intervention: Rescue Medication (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to approximately 81 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) as assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be assessed by Blinded Independent Central Review (BICR). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.
Number of participants who experience one or more adverse events (AEs)
Time Frame: Up to approximately 81 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Objective Response Rate (ORR)
Time Frame: Up to approximately 81 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) as assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be assessed by Blinded Independent Central Review (BICR). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.
Number of participants who experience one or more adverse events (AEs)
Time Frame: Up to approximately 81 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Number of participants who discontinue study intervention due to an AE
Time Frame: Up to approximately 81 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
Secondary Outcomes
- Duration of Response (DOR)(Up to approximately 81 months)
- Progression-free Survival (PFS)(Up to approximately 81 months)
- Overall Survival (OS)(Up to approximately 81 months)
- Overall Survival (OS)(Up to approximately 81 months)
- Duration of Response (DOR)(Up to approximately 81 months)
- Progression-free Survival (PFS)(Up to approximately 81 months)