Trial Outcomes & Findings for M7824 and Topotecan or Temozolomide in Relapsed Small Cell Lung Cancers (NCT NCT03554473)

Last Updated: 2025-05-09

Results Overview

The fraction of evaluable participants who experience a PR or CR will be determined and this fraction will be reported along with an 80% confidence interval. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete response is disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

37 participants

Primary outcome timeframe

6 weeks (Arm B) or 8 weeks (Arm C)

Results posted on

2025-05-09

Participant Flow

Relapsed Small Cell Lung Cancers (SCLC). Extrapulmonary Small Cell Cancer (ESCC).

Participant milestones

Participant milestones
Measure	Arm A/M7824 (MSB0011359C) Monotherapy M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Arm A M7824 Relapsed SCLC STARTED	13	0	0
Arm A M7824 Relapsed SCLC Disease Progression	10	0	0
Arm A M7824 Relapsed SCLC Initial Safety Cohort	7	0	0
Arm A M7824 Relapsed SCLC COMPLETED	10	0	0
Arm A M7824 Relapsed SCLC NOT COMPLETED	3	0	0
Arm B M7824 + Topotecan Relapsed SCLC STARTED	0	5	0
Arm B M7824 + Topotecan Relapsed SCLC Initial Safety Cohort	0	0	0
Arm B M7824 + Topotecan Relapsed SCLC COMPLETED	0	5	0
Arm B M7824 + Topotecan Relapsed SCLC NOT COMPLETED	0	0	0
Arm C M7824 + Temozolomide Relapsed SCLC STARTED	0	0	10
Arm C M7824 + Temozolomide Relapsed SCLC Initial Safety Cohort	0	0	6
Arm C M7824 + Temozolomide Relapsed SCLC COMPLETED	0	0	10
Arm C M7824 + Temozolomide Relapsed SCLC NOT COMPLETED	0	0	0
Arm C M7824 + Temozolomide ESCC STARTED	0	0	9
Arm C M7824 + Temozolomide ESCC COMPLETED	0	0	5
Arm C M7824 + Temozolomide ESCC NOT COMPLETED	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A/M7824 (MSB0011359C) Monotherapy M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Arm A M7824 Relapsed SCLC Withdrew for hospice care.	2	0
Arm A M7824 Relapsed SCLC Worsening brain metastases. Did not complete a full cycle or return for restaging.	1	0
Arm C M7824 + Temozolomide ESCC Developed progressive disease during Cycle 1. Did not complete a full cycle or return for restaging.	0	4

Baseline Characteristics

M7824 and Topotecan or Temozolomide in Relapsed Small Cell Lung Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=13 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=19 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants	22 Participants n=4 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	15 Participants n=4 Participants
Age, Continuous	64.85 years STANDARD_DEVIATION 11 • n=5 Participants	62.6 years STANDARD_DEVIATION 9.71 • n=7 Participants	59 years STANDARD_DEVIATION 12.45 • n=5 Participants	61.54 years STANDARD_DEVIATION 11.65 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants	23 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants	36 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	13 participants n=5 Participants	5 participants n=7 Participants	19 participants n=5 Participants	37 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 weeks (Arm B) or 8 weeks (Arm C)

Population: 7/37 participants were not analyzed because 7 participants were not evaluable for response. They did not complete a full cycle followed by restaging.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=10 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=15 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Proportion of Evaluable Participants Who Experience a Partial Response (PR) or Complete Response (CR) Reported Along With an 80% Confidence Interval. Partial Response	0.1 Proportion of participants Interval 0.0 to 0.2216	0 Proportion of participants Interval 0.0 to 0.0	0.2 Proportion of participants Interval 0.067 to 0.3324
Proportion of Evaluable Participants Who Experience a Partial Response (PR) or Complete Response (CR) Reported Along With an 80% Confidence Interval. Complete Response	0 Proportion of participants Interval 0.0 to 0.0	0 Proportion of participants Interval 0.0 to 0.0	0 Proportion of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 6 weeks (Arm B) or 8 weeks (Arm C)

Population: 7/37 participants were not analyzed because 7 participants were not evaluable for response. They did not complete a full cycle followed by restaging.

The fraction of evaluable participants who experience a PR or CR will be determined and this fraction will be reported along with an 95% confidence interval. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete response is disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=10 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=15 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Proportion of Evaluable Participants Who Experience a Partial Response (PR) or Complete Response (CR) Reported Along With an 95% Confidence Interval. Partial Response	0.1 Proportion of participants Interval 0.0 to 0.2859	0 Proportion of participants Interval 0.0 to 0.0	0.2 Proportion of participants Interval 0.0 to 0.4024
Proportion of Evaluable Participants Who Experience a Partial Response (PR) or Complete Response (CR) Reported Along With an 95% Confidence Interval. Complete Response	0 Proportion of participants Interval 0.0 to 0.0	0 Proportion of participants Interval 0.0 to 0.0	0 Proportion of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 3 weeks for Arm A; First cycle (Arm B - 3 weeks and Arm C- 4 weeks)

Population: 16/37 participants were not analyzed. 3 participants did not complete Cycle 1 and were replaced, and according to the protocol, DLTs were to be assessed in the first 6 participants. If 0 or 1 DLT occurred, treatment would continue at that dose for the remaining participants. Since only 1 DLT was observed in the first 6 participants, the dose was deemed acceptable, and the remaining 13 participants were treated at the same dose without further DLT analysis.

Fraction of participants experiencing a dose-limiting toxicity (DLT) by grade and type assessed by the CTCAE. Grade 3 is severe. Grade 4 is life threatening. Grade 5 is death related to adverse event. The occurrence of any of the following toxicities will be considered a DLT if judged by the Investigator to be possibly, probably or definitely related to study drug administration: Grade 4 non-hematologic toxicity (not laboratory). Grade 4 hematologic toxicity lasting ≥7 days. Grade 3 non-hematologic toxicity (not laboratory, specifically nausea, vomiting and diarrhea) lasting \>5 days despite optimal supportive care. Febrile neutropenia Grade 3 or Grade 4. Thrombocytopenia \<25,000/mm3 if associated with a bleeding event which does not result in hemodynamic instability but requires an elective platelet transfusion, or a life-threatening bleeding event which results in urgent intervention.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=10 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=6 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Number of Participants Experiencing a Dose-limiting Toxicity (DLT) by Grade and Type Grade 3 Rash maculopapular	0 Participants	0 Participants	1 Participants
Number of Participants Experiencing a Dose-limiting Toxicity (DLT) by Grade and Type Grade 4 Platelet count decreased	0 Participants	1 Participants	0 Participants
Number of Participants Experiencing a Dose-limiting Toxicity (DLT) by Grade and Type Grade 5 Death related to adverse event	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Document adverse events from the first study intervention through 30 days after the participant received the last study treatment administration, approximately 30-353 days

Safety of the agent will be assessed by determining the grade of adverse events noted in each participant and reporting the fraction with grade 3 and/or grade 4 adverse events. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 3 is severe. Grade 4 is life-threatening.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=13 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=19 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Proportion of Grade 3 and/or Grade 4 Adverse Events Grade 3	0.149 Proportion of adverse events	0.246 Proportion of adverse events	0.1191 Proportion of adverse events
Proportion of Grade 3 and/or Grade 4 Adverse Events Grade 4	0.01 Proportion of adverse events	0.03 Proportion of adverse events	0.0255 Proportion of adverse events

SECONDARY outcome

Timeframe: At 6 months

Population: 7/37 participants were not analyzed because 7 participants were not evaluable for response.

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. PFS will begin at the on-study date and will consider progressions as well as death without progression as an event. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. PFS was measured using the Kaplan-Meier method and is reported along with a 95% confidence interval.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=10 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=15 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Progression Free Survival (PFS)	2.31 Months Interval 1.38 to 6.5	1.44 Months Interval 1.11 to 2.03	2.03 Months Interval 1.84 to 5.79

SECONDARY outcome

Timeframe: At 6 months

Population: 33/37 participants evaluable for CR/PR were analyzed.

Duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented using the Kaplan-Meier method and reported along with a 95% confidence interval. Response is measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=1 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=3 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Duration of Response (DOR)	3.71 Months A 95% confidence interval cannot be calculated from just one observation because there is no way to estimate variability or the spread of the data.	—	16.67 Months Interval 3.91 to 17.11

SECONDARY outcome

Timeframe: maximum of 67.14 months

Population: 7/37 participants were not analyzed because 7 participants were not evaluable for response.

OS is defined as the date of on-study to the date of death from any cause or last follow up. OS was measured using the Kaplan-Meier method and is reported along with a 95% confidence interval.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=10 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=15 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Overall Survival (OS)	4.58 Months Interval 2.13 to 12.78	2.89 Months Interval 1.87 to 5.88	8.86 Months Interval 2.95 to 17.31

OTHER_PRE_SPECIFIED outcome

Timeframe: Adverse Events was monitored/assessed from the first study intervention through 30 days after the participant received last study treatment administration, 30 - 467 days or an average of 112.4 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Arm A/M7824 (MSB0011359C) Monotherapy n=13 Participants M7824 (MSB0011359C) intravenous (IV) monotherapy once every 21 days on a 21-day cycle. If patients have progressive disease on arm A, they may receive combination therapy of M7824 and Temozolomide. First 7 patients on Arm A received dose of 1800mg intravenous (IV) over 60 minutes M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.	Arm B/M7824 (MSB0011359C) Plus Topotecan n=5 Participants M7824 (MSB0011359C) intravenous (IV) on day 1 plus topotecan (IV) on days 1-5 of a 21-day cycle. At least 6 subjects to receive M7824 plus topotecan to determine safety. 4 more patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 subjects enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Topotecan: Arm B: 1 mg/m(2) intravenous (IV) over 30 minutes days 1-5 on a 3-week cycle.	Arm C/M7824 (MSB0011359C) Plus Temozolomide n=19 Participants M7824 (MSB0011359C) intravenous (IV) days 1 and 15 plus temozolomide (oral) on days 1-5 of a 28-day cycle. At least 6 subjects with small cell lung cancer (SCLC) to receive M7824 plus temozolomide to determine safety. 4 more SCLC patients enrolled at initial or lower dose for efficacy. If efficacious, an additional 12 SCLC subjects enrolled. After the 6 safety SCLC cohort, 10 subjects with extrapulmonary small cell cancers will be enrolled. M7824: Arm A \& B: 2400mg intravenous (IV) over up to 120 minutes every 3 weeks on a 3-week cycle. Arm C: 1200 mg IV over 1 hour every 2 weeks on a 4-week cycle. Temozolomide: Arm C and progressive disease patients on Arm A: 200 mg/m(2) by mouth (PO) days 1-5 on a 4-week cycle.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).	13 Participants	5 Participants	19 Participants

Adverse Events

Arm A/M7824 (MSB0011359C) Monotherapy

Serious events: 8 serious events

Other events: 13 other events

Deaths: 13 deaths

Arm B/M7824 (MSB0011359C) Plus Topotecan

Serious events: 1 serious events

Other events: 5 other events

Deaths: 5 deaths

Arm C/M7824 (MSB0011359C) Plus Temozolomide

Serious events: 12 serious events

Other events: 19 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Anish Thomas

National Cancer Institute

Phone: 2407607343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place