Phase 2
Completed N=76
Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)
Source: ClinicalTrials.gov NCT04768296 ↗Enrolled (actual)
76
Serious AEs
40.8%
Results posted
Sep 2024
Primary outcomePrimary: Main Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) — 5.5 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Main Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC) |
5.5 | — |
| PRIMARY Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0 | — |
| PRIMARY Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs |
3; 3; 3; 3 | — |
| PRIMARY Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
0; 0 | — |
| PRIMARY Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings |
0; 0 | — |
| PRIMARY Safety Run-in Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) |
0; 3; 0; 0 | — |
| SECONDARY 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) |
8.5; 2.8; 2.6; 2.1 | — |
| SECONDARY 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) |
2.2 | — |
| SECONDARY Main Part: Overall Survival (OS) |
6.4 | — |
| SECONDARY 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) |
-4.0 | — |
| SECONDARY 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) |
6; 20; 7; 7; 22; 4 | — |
| SECONDARY 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) |
-6.3 | — |
| SECONDARY Main Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs |
73; 67 | — |
| SECONDARY Main Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
— | — |
| SECONDARY Main Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings |
— | — |
| SECONDARY Main Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) |
18; 17; 28; 26; 19; 2 | — |
| SECONDARY Safety Run-in Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator |
33.3; 0.0 | — |
| SECONDARY Safety Run-in Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator |
7.2 | — |
| SECONDARY Safety Run-in Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator |
14.3; 3.3 | — |
| SECONDARY Safety Run-in Part: Overall Survival (OS) |
NA; 15.3 | — |
| SECONDARY 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) |
— | — |
| SECONDARY 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) |
— | — |
| SECONDARY 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) |
— | — |
| SECONDARY Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of Berzosertib |
2330; 4090 | — |
| SECONDARY 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 |
12.2; 11.1 | — |
| SECONDARY Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib |
2460; 4310 | — |
| SECONDARY Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of Berzosertib |
12.8; 11.7 | — |
| SECONDARY Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours (AUC0-48h) of Berzosertib |
2160; 3790 | — |
| SECONDARY Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 48 Hours (AUC0-48h/Dose) of Berzosertib |
11.3; 10.3 | — |
| SECONDARY Safety Run-in Part: Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72h) of Berzosertib |
2340; 4110 | — |
| SECONDARY Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72h/Dose) of Berzosertib |
12.2; 11.2 | — |
| SECONDARY Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Berzosertib |
259; 446 | — |
| SECONDARY Safety Run-in Part: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of Berzosertib |
1.35; 1.21 | — |
| SECONDARY Safety Run-in Part: Plasma Observed Concentration at the End of the Infusion (Ceoi) of Berzosertib |
259; 446; 341; 500 | — |
| SECONDARY Safety Run-in Part: Plasma Observed Concentration Immediately Before Next Dosing (Ctrough) of Berzosertib |
4.84; 8.57 | — |
| SECONDARY Safety Run-in Part: Apparent Total Body Clearance (CL) of Berzosertib |
77.8; 85.4 | — |
| SECONDARY Safety Run-in Part: Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Berzosertib |
1.32; 1.12 | — |
| SECONDARY Safety Run-in Part: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Berzosertib |
1.17; 1.20 | — |
| SECONDARY Safety Run-in Part: Apparent Terminal Half-life (t1/2) of Berzosertib |
17.6; 17.0 | — |
| SECONDARY Safety Run-in Part: Last Sampling Time (Tlast) of Berzosertib |
70.4; 70.6 | — |
| SECONDARY Safety Run-in Part: Apparent Volume of Distribution During Terminal Phase (Vz) of Berzosertib |
1980; 2100 | — |
Eligibility Criteria
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 ( =) 70 percent (%)
- Dose level 2 and main part participants with ECOG PS = 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 ( =] 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
Data sourced from ClinicalTrials.gov (NCT04768296). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.