This study is a rolling arm study of investigational agents as monotherapy or in combination with pembrolizumab in participants with anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) refractory ES-SCLC in need of second-line treatment. This study will have 2 parts: an initial safety lead-in to determine safety and tolerability for experimental combinations of investigational agents without an established recommended phase 2 dose (RP2D) followed by an efficacy evaluation. Investigational agents will initiate directly in or be added to the efficacy evaluation after an initial evaluation of safety and tolerability of the investigational agent has been completed in a separate study or in the safety lead-in of this study. If an RP2D for a combination being evaluated in the safety lead-in is established from another study, then the efficacy evaluation may begin at the determined RP2D. There will be no hypothesis testing in this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
Intravenous (IV) infusion
Oral administration
IV infusion
IV infusion
IV Infusion
Banner MD Anderson Cancer Center ( Site 0152)
Gilbert, Arizona, United States
Northside Hospital-Northside Hospital Oncology Network ( Site 0156)
Atlanta, Georgia, United States
Parkview Research Center at Parkview Regional Medical Center ( Site 0180)
Fort Wayne, Indiana, United States
Baptist Health Lexington-Research ( Site 0158)
Lexington, Kentucky, United States
University of Kentucky Chandler Medical Center-Medical Oncology ( Site 0157)
Lexington, Kentucky, United States
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLTs = ≥1 of the following treatment-related toxicities: Grade (G)4 nonhematologic toxicity; G4 hematologic toxicity lasting \>7 days OR G4 platelet count decreased OR G3 platelet count decreased if associated with bleeding; G3 nonhematologic toxicity including G3 fatigue (lasting \>3 days), G3 diarrhea, nausea, vomiting lasting ≥72 hours, G3 rash ≥7 days despite treatment, G3 uncontrolled hypertension; G3/4 nonhematologic laboratory abnormality if requires medical intervention, hospitalization, or persists for \>1 week; G 3/4 febrile neutropenia, alanine aminotransferase, aspartate aminotransferase and/or bilirubin increase; drug-induced liver injury meeting the Hy's law; G4 creatinine increase; G4 electrolyte abnormalities; treatment related adverse event causing study intervention discontinuation during the first 21 days or administration delay \>14 days during the first 21 days; G5 toxicity. The number of participants with ≥1 DLTs in the safety lead-in phase will be presented.
Time frame: Up to 21 days in Cycle 1 (Cycle 1 = 21 days)
Number of Participants Who Experience at Least One Adverse Event (AE)
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. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience at least one AE will be presented.
Time frame: Up to approximately 60 months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
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. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be presented.
Time frame: Up to approximately 60 months
Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
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) per RECIST 1.1 that has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time frame: Up to approximately 60 months
Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
PFS is defined as the time from randomization to the first radiographic disease progression (PD) or death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by blinded independent central review (BICR) will be presented.
Time frame: Up to approximately 60 months
Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
For participants who demonstrate a confirmed 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), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time frame: Up to approximately 60 months
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MFSMC-HJWCI-Oncology Research ( Site 0178)
Baltimore, Maryland, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0172)
Omaha, Nebraska, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0179)
Omaha, Nebraska, United States
Cleveland Clinic-Taussig Cancer Center ( Site 0166)
Cleveland, Ohio, United States
UPMC Hillman Cancer Center ( Site 0177)
Pittsburgh, Pennsylvania, United States
...and 38 more locations