Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)

Sponsor
EMD Serono Research & Development Institute, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04768296
Collaborator
Merck KGaA, Darmstadt, Germany (Industry)
86
48
1
35.5
1.8
0.1

Study Details

Study Description

Brief Summary

The main purpose of this study is to assess efficacy, safety, tolerability and pharmacokinetics (PK) of Berzosertib in combination with Topotecan in participants with relapsed, platinum-resistant small-cell lung cancer (SCLC). This study will be conducted in two parts: safety run-in part and main part. The safety run-in part will be conducted in Japan.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
86 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Mar 29, 2021
Anticipated Primary Completion Date :
Mar 13, 2023
Anticipated Study Completion Date :
Mar 13, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Berzosertib + Topotecan

In Japan, a Safety Run-in Part will be conducted. In case safety and tolerability is confirmed in the Safety Run-in part, Japanese participants will enroll in the Main Part of the Phase 2. Both in the Safety Run-in and Main Part of the Phase 2, participants will receive berzosertib and topotecan until disease progression or other criteria for study intervention discontinuation are met.

Drug: Berzosertib
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.
Other Names:
  • M6620
  • Drug: Berzosertib
    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.
    Other Names:
  • M6620
  • Drug: 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.

    Outcome Measures

    Primary Outcome Measures

    1. Main Part: Objective Response (OR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 as assessed by Independent Review Committee (IRC) [From first administration of study intervention up to 15 months]

    2. Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs) [Up to Cycle 1 Day 21 (each cycle is of 21 days)]

    3. Safety Run-in Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs [From first administration of study intervention up to 15 months]

    4. Safety Run-in Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters [From first administration of study intervention up to 15 months]

    Secondary Outcome Measures

    1. Main Part: Duration of Response (DoR) according to RECIST version 1.1 as assessed by IRC [From first administration of study intervention up to 15 months]

    2. Main Part: Progression-free Survival (PFS) according to RECIST version 1.1 as assessed by IRC [From first administration of study intervention up to 15 months]

    3. Main Part: Overall Survival (OS) [From first administration of study intervention up to 15 months]

    4. Main Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [Baseline, Safety follow-up (up to 15 months)]

    5. Main Part: Change From Baseline in Cough, Dyspnea and Chest Pain Measured by European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) [Baseline, Safety follow-up (up to 15 months)]

    6. Main Part:Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) [Baseline, Safety follow-up (up to 15 months)]

    7. Main Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs [From first administration of study intervention up to 15 months]

    8. Main Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters [From first administration of study intervention up to 15 months]

    9. Safety Run-in Part: Objective response according to RECIST version 1.1 as assessed by the Investigator [From first administration of study intervention up to 15 months]

    10. Safety Run-in Part: Duration of Response (DoR) according to RECIST version 1.1 as assessed by the Investigator [From first administration of study intervention up to 15 months]

    11. Safety Run-in Part: Progression-free Survival (PFS) according to RECIST version 1.1 as assessed by the Investigator [From first administration of study intervention up to 15 months]

    12. Safety Run-in Part: Overall Survival (OS) [From first administration of study intervention up to 15 months]

    13. Safety Run-in Part: Change From Baseline in Cough, Dyspnea and Chest Pain Measured by European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) [Baseline, Safety follow-up (up to 15 months)]

    14. Safety Run-in Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [Baseline, Safety follow-up (up to 15 months)]

    15. Safety Run-in Part:Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) [Baseline, Safety follow-up (up to 15 months)]

    16. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (AUC0-tlast) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    17. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    18. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    19. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    20. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to 48 Hours (AUC0-48h) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    21. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to 48 Hours (AUC0-48h/Dose) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    22. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to 72 Hours (AUC0-72h) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    23. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to 72 Hours (AUC0-72h/Dose) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    24. Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    25. Safety Run-in Part: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    26. Safety Run-in Part: Plasma Observed Concentration at the End of the Infusion (Ceoi) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    27. Safety Run-in Part: Plasma Observed Concentration Immediately Before Next Dosing (Ctrough) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    28. Safety Run-in Part: Apparent Total Body Clearance (CL) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    29. Safety Run-in Part: Metabolic Ratio of Maximum Observed Plasma Concentration (MR[Cmax]) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    30. Safety Run-in Part: Metabolic Ratio of Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (MR[AUC0-tlast]) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    31. Safety Run-in Part: Metabolic Ratio Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (MR[AUC0-inf]) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    32. Safety Run-in Part: Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    33. Safety Run-in Part: Time to Reach the Maximum Observed Plasma Concentration (tmax) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    34. Safety Run-in Part: Apparent Terminal Half-life (t1/2) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    35. Safety Run-in Part: Last Sampling Time (tlast) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    36. Safety Run-in Part: Apparent Volume of Distribution (Vz) of Berzosertib [23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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

    Exclusion Criteria:
    • 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 2 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Providence Medical Foundation Santa Rosa California United States 95403
    2 St Joseph Heritage Healthcare Santa Rosa California United States 95403
    3 Cotton-O'Neil Clinical Research Center, Hematology and Oncology Topeka Kansas United States 66606
    4 National Cancer Institute Bethesda Maryland United States 20892
    5 Cancer & Hematology Centers of Western Michigan Grand Rapids Michigan United States 49546
    6 MidAmerica Cancer Care Kansas City Missouri United States 64114
    7 Southeastern Medical Oncology Center Goldsboro North Carolina United States 27534
    8 FirstHealth of the Carolinas, Inc. Pinehurst North Carolina United States 28374
    9 Summa Health Akron Ohio United States 44304
    10 Toledo Clinic Toledo Ohio United States 43623
    11 Millennium Physicians Association, LLP Houston Texas United States 77090
    12 Centre Hospitalier de l'Ardenne Arlon Belgium
    13 Institut Jules Bordet - Department of Institut Jules Bordet Brussels Belgium 1000
    14 Universitair Ziekenhuis Gent Gent Belgium 9000
    15 AZ Delta Roeselare Belgium 8800
    16 CHU UCL Namur - Mont-Godinne Yvoir Belgium 5530
    17 The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China
    18 Beijing Cancer Hospital Beijing China
    19 Jilin Cancer Hospital Changchun China 130000
    20 Sichuan Cancer Hospital Chengdu China 610041
    21 West China Hospital, Sichuan University Chengdu China 610041
    22 Jiangsu Province Hospital Nanjing China
    23 Union Hospital of Tongji Medical College, Huazhong University of Science and Technology Wuhan China 430023
    24 The First Affiliated Hospital of Zhejiang University school of medicine Zhejiang China 310003
    25 Institut Bergonié Bordeaux cedex France 33076
    26 Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie Créteil France 94010
    27 Hopital Albert Calmette - CHU Lille - service de pneumologie et immuno allergologie Lille France 59037
    28 CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale Poitiers France 86021
    29 CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie Saint-Herblain France 44805
    30 CHU de Strasbourg - Nouvel Hôpital Civil - Service de Pneumologie Strasbourg France 67091
    31 IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST Meldola Italy 47014
    32 Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda) Milano Italy 20162
    33 Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello) Pisa Italy 56124
    34 Istituto Nazionale Tumori Regina Elena IRCCS Roma Italy 00144
    35 Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica Rome Italy 00168
    36 National Cancer Center Hospital Chuo-ku Japan 104-0045
    37 Kansai Medical University Hospital Hirakata-shi Japan 573-1191
    38 National Cancer Center Hospital East Kashiwa-shi Japan 277-8577
    39 Cancer Institute Hospital of JFCR Koto-ku Japan 135-8550
    40 Kindai University Hospital Osaka Japan
    41 Kurume University Hospital Osaka Japan
    42 Osaka Medical and Pharmaceutical University Hospital Takatsuki-shi Japan 569-8686
    43 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    44 Hospital Clinic de Barcelona Barcelona Spain 08036
    45 Hospital Universitario 12 de Octubre Madrid Spain 28041
    46 Hospital Universitario La Paz Madrid Spain 28046
    47 Hospital Universitario Virgen de la Victoria Malaga Spain
    48 Hospital Universitario Virgen Macarena Sevilla Spain 41009

    Sponsors and Collaborators

    • EMD Serono Research & Development Institute, Inc.
    • Merck KGaA, Darmstadt, Germany

    Investigators

    • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    EMD Serono Research & Development Institute, Inc.
    ClinicalTrials.gov Identifier:
    NCT04768296
    Other Study ID Numbers:
    • MS201923_0050
    • 2020-004231-25
    First Posted:
    Feb 24, 2021
    Last Update Posted:
    Jun 27, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by EMD Serono Research & Development Institute, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 27, 2022