Trial Outcomes & Findings for DS-3201b and Irinotecan for Patients With Recurrent Small Cell Lung Cancer (NCT NCT03879798)
NCT ID: NCT03879798
Last Updated: 2024-10-10
Results Overview
Will employ a standard 3-by-3 dose-escalation phase I study design to investigate the maximum tolerated dose (MTD) of DS-3201b/valemetostat in combination with fixed dose irinotecan. The study population for Phase I dose-escalation will include only patients who complete at least 1 full cycle of treatment (including the initial 7-day safety run-in and the complete 21-days of Cycle 1); only these patients will be considered evaluable for DLT and determination of the MTD.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
22 participants
Primary outcome timeframe
1 year
Results posted on
2024-10-10
Participant Flow
Participant milestones
| Measure |
Phase I, Dose Level 1
Dose Level 1 (DS-3201b 100mg)
|
Phase I, Dose Level 2
Dose Level 2 (DS-3201b 150mg)
|
Phase I, Dose Level 3
Dose Level 3 (DS-3201b 200mg)
|
Phase I, Dose Level 4
Dose Level 4 (DS-3201b 250mg)
|
Phase I, Dose Level 5
Dose Level 5 (DS-3201b 300mg)
|
Phase 2
DS-3201b 100mg
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
0
|
0
|
0
|
10
|
|
Overall Study
COMPLETED
|
6
|
6
|
0
|
0
|
0
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
3
|
Reasons for withdrawal
| Measure |
Phase I, Dose Level 1
Dose Level 1 (DS-3201b 100mg)
|
Phase I, Dose Level 2
Dose Level 2 (DS-3201b 150mg)
|
Phase I, Dose Level 3
Dose Level 3 (DS-3201b 200mg)
|
Phase I, Dose Level 4
Dose Level 4 (DS-3201b 250mg)
|
Phase I, Dose Level 5
Dose Level 5 (DS-3201b 300mg)
|
Phase 2
DS-3201b 100mg
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
DS-3201b and Irinotecan for Patients With Recurrent Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Phase I, Dose Level 1
n=6 Participants
Dose Level 1 (DS-3201b 100mg)
|
Phase I, Dose Level 2
n=6 Participants
Dose Level 2 (DS-3201b 150mg)
|
Phase I, Dose Level 3
Dose Level 3 (DS-3201b 200mg)
|
Phase I, Dose Level 4
Dose Level 4 (DS-3201b 250mg)
|
Phase I, Dose Level 5
Dose Level 5 (DS-3201b 300mg)
|
Phase 2
n=10 Participants
DS-3201b 100mg
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
72 years
n=5 Participants
|
59 years
n=7 Participants
|
—
|
—
|
—
|
67 years
n=8 Participants
|
66 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
—
|
—
|
—
|
7 Participants
n=8 Participants
|
13 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
—
|
—
|
—
|
3 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
—
|
—
|
—
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
—
|
—
|
—
|
0 Participants
n=8 Participants
|
10 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
10 Participants
n=8 Participants
|
11 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
—
|
—
|
—
|
7 Participants
n=8 Participants
|
19 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
—
|
1 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
—
|
—
|
—
|
10 Participants
n=8 Participants
|
22 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: MTD determined from phase I
Will employ a standard 3-by-3 dose-escalation phase I study design to investigate the maximum tolerated dose (MTD) of DS-3201b/valemetostat in combination with fixed dose irinotecan. The study population for Phase I dose-escalation will include only patients who complete at least 1 full cycle of treatment (including the initial 7-day safety run-in and the complete 21-days of Cycle 1); only these patients will be considered evaluable for DLT and determination of the MTD.
Outcome measures
| Measure |
All Phase I Participants, Dose Level 1 & Dose Level 2
n=10 Participants
Dose Level 1 (DS-3201b 100mg)
Dose Level 2 (DS-3201b 150mg)
|
Phase 2
The first part of this study is a phase I trial to assess the safety and tolerability of DS-3201b in combination with fixed-dose irinotecan. The second part of this study will be an open label, single-arm phase II study of DS-3201b at the established recommended phase II dose (RP2D) in combination with fixed-dose irinotecan. Dose-Escalation, which enrolled a total of 12 patients at MSK, is completed. Phase 1 of this study determined that the highest and safest dose of DS-3201b in patients was 100 mg daily.
DS-3201b: 100 mg daily
irinotecan: Irinotecan 125 mg/m\^2 intravenously on days 1 and 8 every 3 weeks in a 21-day cycle.
|
|---|---|---|
|
Maximum Tolerated Dose (MTD) (Phase l) of DS-3201/Valemetostat
|
100 mg
|
—
|
PRIMARY outcome
Timeframe: 1 yearPopulation: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
The Response Evaluation Criteria in Solid Tumors Group (RECIST v1.1) criteria will be used to evaluate the response to treatment
Outcome measures
| Measure |
All Phase I Participants, Dose Level 1 & Dose Level 2
Dose Level 1 (DS-3201b 100mg)
Dose Level 2 (DS-3201b 150mg)
|
Phase 2
n=10 Participants
The first part of this study is a phase I trial to assess the safety and tolerability of DS-3201b in combination with fixed-dose irinotecan. The second part of this study will be an open label, single-arm phase II study of DS-3201b at the established recommended phase II dose (RP2D) in combination with fixed-dose irinotecan. Dose-Escalation, which enrolled a total of 12 patients at MSK, is completed. Phase 1 of this study determined that the highest and safest dose of DS-3201b in patients was 100 mg daily.
DS-3201b: 100 mg daily
irinotecan: Irinotecan 125 mg/m\^2 intravenously on days 1 and 8 every 3 weeks in a 21-day cycle.
|
|---|---|---|
|
Objective Response Rate (ORR) (Phase II)
|
—
|
21 % of participants
Interval 6.0 to 46.0
|
Adverse Events
Phase I, Dose Level 1
Serious events: 0 serious events
Other events: 6 other events
Deaths: 6 deaths
Phase I, Dose Level 2
Serious events: 0 serious events
Other events: 6 other events
Deaths: 5 deaths
Phase I, Dose Level 3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase I, Dose Level 4
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase I, Dose Level 5
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 2
Serious events: 0 serious events
Other events: 10 other events
Deaths: 8 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Phase I, Dose Level 1
n=6 participants at risk
Dose Level 1: 100mg
|
Phase I, Dose Level 2
n=6 participants at risk
Dose Level 2: 150mg
|
Phase I, Dose Level 3
Dose Level 3: 200mg
|
Phase I, Dose Level 4
Dose Level 4: 250mg
|
Phase I, Dose Level 5
Dose Level 5: 300mg
|
Phase 2
n=10 participants at risk
Dose Level 2: 100mg
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
83.3%
5/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
66.7%
4/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
60.0%
6/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
General disorders
Fatigue
|
50.0%
3/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
66.7%
4/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
40.0%
4/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
50.0%
3/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
30.0%
3/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
50.0%
3/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
50.0%
5/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
66.7%
4/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
33.3%
2/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
10.0%
1/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Metabolism and nutrition disorders
Anorexia
|
66.7%
4/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
33.3%
2/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
0.00%
0/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.7%
1/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
33.3%
2/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
20.0%
2/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
50.0%
3/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
10.0%
1/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
16.7%
1/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
30.0%
3/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
2/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
16.7%
1/6 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
—
0/0 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
10.0%
1/10 • 1 year
Participants were not treated on Dose Level 3, 4 or 5
|
Additional Information
Dr. Charles Rudin
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4527
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place