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

NCT04768296 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MS201923_00502020-004231-25
• Study Type: interventional
• Target: 76
• Locations: 7 countries
• Sites: 51

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.

Conditions

Small-cell Lung Cancer

Keywords

M6620; Berzosertib; Solid Tumor; Topotecan; Ataxia telangiectasia mutated and Rad3-related; Platinum-resistant Small-Cell Lung Cancer; DDRiver

Outcome Measures

Primary Outcomes (6)

• Main Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC)

  Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion.

  Time from first administration of study treatment up to 27.7 months

• Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT is defined as drug-related: Neutropenia Grade 4 for greater than (\>) 7 days' duration; Febrile neutropenia (that is \[i.e.\] absolute neutrophil count less than (\< ) 1000 per millimeter cube (mm\^3) with single temperature of \> 38.3°degree Celsius or a sustained temperature of greater than or equal to (\>=) 38 degree Celsius for more than 1 hour; Infection (documented clinically or microbiologically) with Grades 3 or 4 neutropenia; Thrombocytopenia \>= Grade 3; Grade \>= 3 non-hematological AEs.

  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) and Treatment-Related TEAEs

  An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention.

  Time from first administration of study treatment up to 27.7 months

• Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

  Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinical significance was decided by Investigator.

  Time from first administration of study treatment up to 27.7 months

• Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings

  ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant changes from baseline in 12-Lead ECGs were reported.

  Time from first administration of study treatment up to 27.7 months

• Safety Run-in Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)

  The laboratory measurements included hematology and biochemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (\>=) 3 in laboratory values reported as TEAEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Clinically Significance was decided by investigator.

  Time from first administration of study treatment up to 27.7 months

Secondary Outcomes (35)

• Main Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC)

  From first documented objective response to PD or death due to any cause, assessed up to 27.7 months

• Main Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC)

  Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed up to 27.7 months

• Main Part: Overall Survival (OS)

  Time from first administration of study treatment to the date of death, assessed up to 27.7 months

• 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 (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days

• Main Part: Number of Participants Who Improved, Worsened or Remained Stable in European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13)

  Baseline (Cycle 1 Day 1), end of treatment (up to 62 weeks). Each cycle is of 21 days

Study Arms (2)

Safety run-in Part (Dose Level1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2

EXPERIMENTAL

Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m\^2 ) intravenously on Day 2 and Day 5 of each 21-daycycle in combination with Topotecan at a dose of 1.25mg/m\^2 intravenously on Days1 through 5 of each 21-day cycle in DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met.

Drug: Berzosertib; Drug: Topotecan

Safety run-in Part (DL2) +Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2

EXPERIMENTAL

Participants received Berzosertib at a dose of 210 mg/m\^2 intravenously on Day 2 and Day 5 of each 21-day cycle in combination with Topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in DL 1 and DL 2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.

Drug: Berzosertib; Drug: Topotecan

Interventions

Berzosertib DRUG

Participants received 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 until disease progression or other criteria for study intervention discontinuation are met.

Also known as: M6620

Safety run-in Part (Dose Level1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2

Topotecan DRUG

Participants received 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.

Safety run-in Part (DL2) +Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2; Safety run-in Part (Dose Level1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (51)

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

St Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Cotton-O'Neil Clinical Research Center, Hematology and Oncology

Topeka, Kansas, 66606, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49546, United States

Location

MidAmerica Cancer Care

Kansas City, Missouri, 64114, United States

Location

NJ Center for Cancer Research

Brick, New Jersey, 08724, United States

Location

Southeastern Medical Oncology Center

Goldsboro, North Carolina, 27534, United States

Location

FirstHealth of the Carolinas, Inc.

Pinehurst, North Carolina, 28374, United States

Location

Summa Health

Akron, Ohio, 44304, United States

Location

Toledo Clinic

Toledo, Ohio, 43623, United States

Location

Millennium Physicians Association, LLP

Houston, Texas, 77090, United States

Location

Centre Hospitalier de l'Ardenne

Arlon, Belgium

Location

Institut Jules Bordet - Department of Institut Jules Bordet

Brussels, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

AZ Delta

Roeselare, Belgium

Location

CHU UCL Namur - Mont-Godinne

Yvoir, Belgium

Location

Beijing Cancer Hospital

Beijing, China

Location

Jilin Cancer Hospital

Changchun, China

Location

Sichuan Cancer Hospital

Chengdu, China

Location

West China Hospital, Sichuan University

Chengdu, China

Location

Jiangsu Province Hospital

Nanjing, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, China

Location

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

Location

The First Affiliated Hospital of Zhejiang University school of medicine

Zhejiang, China

Location

Institut Bergonié

Bordeaux, France

Location

Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie

Créteil, France

Location

Hopital Albert Calmette - CHU Lille - service de pneumologie et immuno allergologie

Lille, France

Location

CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale

Poitiers, France

Location

CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie

Saint-Herblain, France

Location

CHU de Strasbourg - Nouvel Hôpital Civil - Service de Pneumologie

Strasbourg, France

Location

IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST

Meldola, Italy

Location

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, Italy

Location

Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)

Pisa, 56124, Italy

Location

Istituto Nazionale Tumori Regina Elena IRCCS

Roma, 00144, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

Rome, Italy

Location

National Cancer Center Hospital

Chūōku, Japan

Location

Kansai Medical University Hospital

Hirakata-shi, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Japan

Location

Cancer Institute Hospital of JFCR

Kōtoku, Japan

Location

Kindai University Hospital

Osaka, Japan

Location

Kurume University Hospital

Osaka, Japan

Location

Osaka Medical and Pharmaceutical University Hospital

Takatsuki-shi, Japan

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria - Oncology Service

Málaga, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources
• DDRiver website

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Hereditary Sensory and Autonomic Neuropathies

Interventions

berzosertib; Topotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 24, 2021
• Study Start: March 29, 2021
• Primary Completion: July 21, 2023
• Study Completion: July 21, 2023
• Last Updated: September 26, 2024
• Results First Posted: September 26, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

ES (7); US (12); IT (5); FR (6); CN (9); JP (7); BE (5)