A Phase II, open-label, single-arm study of berzosertib (M6620) in combination with topotecan in participants with relapsed platinum resistant small-cell lung cancer (DDRiver SCLC 250)
Berzosertib+topotecan in relapsed platinum resistant SCLC (DDRiver SCLC 250)
Yamaki Masataka
Merck Biopharma Co., Ltd.
1-8-1 Shimomeguro, Meguro-ku, Tokyo
+81-80-5409-0077
MBJ_clinicaltrial_information@merckgroup.com
Clinical Trial Information for Contact
Merck Biopharma Co., Ltd.
1-8-1 Shimomeguro, Meguro-ku, Tokyo
+81-3-6756-0800
MBJ_clinicaltrial_information@merckgroup.com
Complete
July. 12, 2021
Aug. 05, 2021
9
Interventional
non-randomized controlled trial
open(masking not used)
uncontrolled control
single assignment
treatment purpose
- Dose level 1 participants with histologically proven advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed or cannot be tolerated
- Dose level 1 participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) less than or equal to (<=) 1 and Karnofsky Scale greater than or equal to (>=) 70 percent (%)
- Dose level 2 and main part participants with ECOG PS <= 2 and Karnofsky Scale >= 60%
- Dose level 2 and main part participants with histologically confirmed SCLC
- Dose level 2 and main part participants with radiologically confirmed progression after first-line or chemoradiation platinum-based treatment (carboplatin or cisplatin), with or without immunotherapy, for treatment of limited or extensive stage SCLC, with a Platinum-free interval (PFI) less than (<) 90 days. The PFI is measured by the elapsed time from the last day of the regimen of a platinum-based treatment until the first day of documented disease progression
- Dose level 2 and main part participants with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (RECISTv1.1) at Screening. Evidence of measurable disease must be confirmed by the IRC prior to start of treatment
- Tumor tissue provision: archival (collected within 12 months before date of informed consent form [ICF]) signature for Screening) or fresh biopsy specimen, if medically feasible
- Have adequate hematologic and renal function
- Other protocol defined inclusion criteria could apply
- Clinically relevant (that is [i.e.], active), uncontrolled intercurrent illness including, but not limited to, severe active infection including, severe acute respiratory syndrome coronavirus-2 infection/coronavirus disease 2019, immune deficiencies, uncontrolled diabetes, uncontrolled arterial hypertension, symptomatic congestive heart failure (New York Heart Association Classification greater than or equal to [>=] Class III), unstable angina pectoris, myocardial infarction, uncontrolled cardiac arrhythmia, cerebral vascular accident/stroke. Calculated corrected QT interval (QTc) average (using the Fridericia correction calculation) of greater than [>] 450 millisecond (msec) for males and > 470 msec for females. Any psychiatric illness/social situations that would limit compliance with study requirements
- Unstable brain metastases; however, participants with known brain metastases may be enrolled in this clinical study if they are clinically stable (without evidence of progression by imaging for at least 4 weeks prior to the first study intervention dose and any neurologic symptoms have returned to baseline), have no evidence of new brain metastases, and are on a stable or decreasing dose of steroids for at least 14 days prior to study intervention Participants with carcinomatous meningitis are excluded regardless of clinical stability. Screening central nervous system imaging is not mandatory
- Prior malignant disease within the last 3 years. Exceptions include fully resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ cervical cancer, fully resected ductal carcinoma in situ of the breast, superficial or noninvasive bladder cancer, and Stage IA, Grade I endometrioid endometrial cancer with no myometrial invasion, that has undergone curative therapy. Participants with other localized malignancies treated with curative intent need to be discussed with the Medical Monitor
- Participants not recovered from adverse events (AEs) Grade > 1 from prior anticancer therapies, including surgeries. Exception: Grade 2 AEs not constituting a safety risk (for example [e.g.], alopecia), based on the Investigator's judgment; must consult with the medical Monitor prior to enrollment.
- Other protocol defined exclusion criteria could apply.
18age old over
No limit
Both
Small-cell Lung Cancer
[Berzosertib (M6620)]
- Participants with advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed will receive Berzosertib at a dose of 105 milligrams per square meter (mg/m^2) intravenously on Day 2 and Day 5 of each 21-day cycle in DL1 of safety run-in part.
- Participants with relapsed, platinum-resistant SCLC will receive Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle in DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.
[Topotecan]
- Participants who have advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed or who have relapsed, platinum-resistant SCLC will receive Topotecan at a dose of 1.25 mg/m^2 intravenously on Days 1 through 5 of each 21-day cycle in DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.
- Main Part: Objective Response (OR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 as assessed by Independent Review Committee (IRC) [ Time Frame: From first administration of study intervention up to 15 months ]
- Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to Cycle 1 Day 21 (each cycle is of 21 days) ]
- Safety Run-in Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs [ Time Frame: From first administration of study intervention up to 15 months ]
- Safety Run-in Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters [ Time Frame: From first administration of study intervention up to 15 months ]
