Trial Outcomes & Findings for Testing the Addition of an Anti-cancer Drug, Berzosertib (M6620, VX-970), to the Usual Treatments (Carboplatin and Gemcitabine) and to Pembrolizumab for Patients With Advanced Squamous Cell Non-small Cell Lung Cancer (NCT NCT04216316)

Last Updated: 2026-04-13

Results Overview

Percentage of patients who experienced Dose Limiting Toxicities (DLTs) when treated with carboplatin in combination with berzosertib (M6620, VX-970), per CTCAE v5.0

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to completion of cycle 1

Results posted on

2026-04-13

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level -1 (Pembrolizumab, Gemcitabine, Carboplatin, M6620) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - 4 AUC Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg The following treatment schedule will be used for a total of two years of treatment. Pembrolizumab administration should not exceed 2 years. * Cycles 1 to 4 (first 3 months of the first year): gemcitabine on D1 and D8, carboplatin and pembrolizumab on D1, and +/- berzosertib (M6620, VX-970) on D2 and D9, every three weeks * Cycles 5 to 16 (last 9 months of the first year): pembrolizumab +/- berzosertib (M6620, VX-970) on D1, every 3 weeks * Cycles 17 to 26 (second year): pembrolizumab on D1, every 6 weeks	Dose Level 1 (Pembrolizumab, Gemcitabine, Carboplatin, M6620) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - 5 AUC Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg The following treatment schedule will be used for a total of two years of treatment. Pembrolizumab administration should not exceed 2 years. * Cycles 1 to 4 (first 3 months of the first year): gemcitabine on D1 and D8, carboplatin and pembrolizumab on D1, and +/- berzosertib (M6620, VX-970) on D2 and D9, every three weeks * Cycles 5 to 16 (last 9 months of the first year): pembrolizumab +/- berzosertib (M6620, VX-970) on D1, every 3 weeks * Cycles 17 to 26 (second year): pembrolizumab on D1, every 6 weeks
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Addition of an Anti-cancer Drug, Berzosertib (M6620, VX-970), to the Usual Treatments (Carboplatin and Gemcitabine) and to Pembrolizumab for Patients With Advanced Squamous Cell Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lead-in Dose Level -1 (Pembrolizumab, Gemcitabine, Carboplatin, M6620) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - 4 AUC Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg The following treatment schedule will be used for a total of two years of treatment. Pembrolizumab administration should not exceed 2 years. * Cycles 1 to 4 (first 3 months of the first year): gemcitabine on D1 and D8, carboplatin and pembrolizumab on D1, and +/- berzosertib (M6620, VX-970) on D2 and D9, every three weeks * Cycles 5 to 16 (last 9 months of the first year): pembrolizumab +/- berzosertib (M6620, VX-970) on D1, every 3 weeks * Cycles 17 to 26 (second year): pembrolizumab on D1, every 6 weeks	Lead-in Dose Level 1 (Pembrolizumab, Gemcitabine, Carboplatin, M6620) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - 5 AUC Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg The following treatment schedule will be used for a total of two years of treatment. Pembrolizumab administration should not exceed 2 years. * Cycles 1 to 4 (first 3 months of the first year): gemcitabine on D1 and D8, carboplatin and pembrolizumab on D1, and +/- berzosertib (M6620, VX-970) on D2 and D9, every three weeks * Cycles 5 to 16 (last 9 months of the first year): pembrolizumab +/- berzosertib (M6620, VX-970) on D1, every 3 weeks * Cycles 17 to 26 (second year): pembrolizumab on D1, every 6 weeks	Total n=12 Participants Total of all reporting groups
Age, Continuous	72.00 years n=193 Participants	60.67 years n=193 Participants	65.5 years n=386 Participants
Sex: Female, Male Female	3 Participants n=193 Participants	4 Participants n=193 Participants	7 Participants n=386 Participants
Sex: Female, Male Male	3 Participants n=193 Participants	2 Participants n=193 Participants	5 Participants n=386 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=193 Participants	2 Participants n=193 Participants	2 Participants n=386 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=193 Participants	4 Participants n=193 Participants	10 Participants n=386 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Asian	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Black or African American	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) White	6 Participants n=193 Participants	5 Participants n=193 Participants	11 Participants n=386 Participants
Race (NIH/OMB) More than one race	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=193 Participants	1 Participants n=193 Participants	1 Participants n=386 Participants
ECOG Performance Score ECOG = 0	2 Score on a scale n=193 Participants	3 Score on a scale n=193 Participants	5 Score on a scale n=386 Participants
ECOG Performance Score ECOG = 1	4 Score on a scale n=193 Participants	3 Score on a scale n=193 Participants	7 Score on a scale n=386 Participants
Tumor Type - Squamous cell lung cancer	6 Participants n=193 Participants	6 Participants n=193 Participants	12 Participants n=386 Participants
Patients with Zero Prior Lines of Therapy for Advanced Disease	6 Participants n=193 Participants	6 Participants n=193 Participants	12 Participants n=386 Participants

PRIMARY outcome

Timeframe: Up to completion of cycle 1

Population: Treated patients evaluated for Dose Limiting Toxicities (DLTs)

Percentage of patients who experienced Dose Limiting Toxicities (DLTs) when treated with carboplatin in combination with berzosertib (M6620, VX-970), per CTCAE v5.0

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Patients Who Experienced a DLT	0 percentage of patients Interval 0.0 to 45.9	33.3 percentage of patients Interval 4.3 to 77.7

PRIMARY outcome

Timeframe: Up to completion of cycle 1

Population: Treated patients evaluated for Dose Limiting Toxicities (DLTs) who received Dose Level -1 (carboplatin dosed at 4 mg/mL\*min)

Determined by the number of patients who experienced Dose Limiting Toxicities (DLTs) when treated with carboplatin in combination with berzosertib (M6620, VX-970), per CTCAE v5.0, DLT is defined as the severe toxicity event that leads to the termination of the treatment. The RP2D is the highest dose level where \<2/6 DLTs are observed.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Recommended Phase 2 Dose (RP2D)	4 mg/mL*min	—

PRIMARY outcome

Timeframe: At 12 months

Population: Treated patients evaluated for radiologic response.

Percentage of patients with Progression-free survival (PFS) will be estimated within disease cohorts by the product-limit (Kaplan-Meier) estimator, along with 95% confidence regions, from start of treatment to time of progression or death, whichever occurs first. Per RECIST v1.1 Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=12 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
12-month Progression-free Survival (PFS) - Total Population	28 percentage of patients Interval 7.0 to 54.0	—

PRIMARY outcome

Timeframe: At 24 months

Population: Treated patients evaluated for radiologic response.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=12 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
24-month Progression-free Survival (PFS) - Total Population	18 percentage of patients Interval 3.0 to 44.0	—

PRIMARY outcome

Timeframe: Up to 30 months

Population: Treated patients evaluated for radiologic response.

Median PFS will be estimated within disease cohorts by the product-limit (Kaplan-Meier) estimator, along with 95% confidence regions. Measured from start of treatment to time of progression or death, whichever occurs first. Per RECIST v1.1 Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=12 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Progression-free Survival (PFS) - Total Population	9.00 months Interval 3.0 to 13.0	—

PRIMARY outcome

Timeframe: At 12 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
12-month Progression-free Survival (PFS) - By Dose Level	20 percentage of patients Interval 1.0 to 58.0	33 percentage of patients Interval 5.0 to 68.0

PRIMARY outcome

Timeframe: At 24 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
24-month Progression-free Survival (PFS) - Dose Level 1	17 percentage of patients Interval 1.0 to 52.0	—

PRIMARY outcome

Timeframe: Up to 30 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Progression-free Survival (PFS) - By Dose Level	9.00 months Interval 3.0 to Upper bound of 95% CI not reached.	8.00 months Interval 0.0 to Upper bound of 95% CI not reached.

SECONDARY outcome

Timeframe: Up to 12 months post treatment

Population: Treated patients evaluated for radiologic response.

Percentage of patients with Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm; PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters or SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=11 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Best Overall Response - Total Population Complete Response (CR)	0 percentage of patients Interval 0.0 to 28.5	—
Best Overall Response - Total Population Partial Response (PR)	45.5 percentage of patients Interval 16.7 to 76.6	—
Best Overall Response - Total Population Stable Disease (SD)	54.5 percentage of patients Interval 23.4 to 83.3	—
Best Overall Response - Total Population Progressive Disease (PD)	0 percentage of patients Interval 0.0 to 28.5	—

SECONDARY outcome

Timeframe: Up to 12 months post treatment

Population: Treated patients evaluated for radiologic response.

Percentage of patients with Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm; PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters or SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=5 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Best Overall Response - By Dose Level Stable Disease (SD)	50 percentage of patients	60 percentage of patients
Best Overall Response - By Dose Level Progressive Disease (PD)	0 percentage of patients	0 percentage of patients
Best Overall Response - By Dose Level Complete Response (CR)	0 percentage of patients	0 percentage of patients
Best Overall Response - By Dose Level Partial Response (PR)	50 percentage of patients	40 percentage of patients

SECONDARY outcome

Timeframe: At 12 months

Population: All treated patients

Percentage of patients alive from start of treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=12 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
12-month Overall Survival (OS) - Total Population	67 percentage of patients Interval 34.0 to 86.0	—

SECONDARY outcome

Timeframe: At 24 months

Population: All treated patients

Percentage of patients alive from start of treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=12 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
24-month Overall Survival (OS) - Total Population	35 percentage of patients Interval 9.0 to 63.0	—

SECONDARY outcome

Timeframe: Up to 30 months post treatment

Population: All treated patients.

Median number of months that patients remain alive from start of treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=12 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Overall Survival (OS) - Total Population	15.00 months Interval 3.0 to Upper bound of 95% CI not reached	—

SECONDARY outcome

Timeframe: At 12 months

Population: All treated patients

Percentage of patients alive from start of treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
12-month Overall Survival (OS) - By Dose Level	67 percentage of patients Interval 20.0 to 90.0	67 percentage of patients Interval 20.0 to 90.0

SECONDARY outcome

Timeframe: At 24 months

Population: All treated patients.

Percentage of patients alive from start of treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
24-month Overall Survival (OS) - By Dose Level	67 percentage of patients Interval 20.0 to 90.0	17 percentage of patients Interval 1.0 to 52.0

SECONDARY outcome

Timeframe: Up to 30 months post treatment

Population: All treated patients.

Median number of months that patients remain alive from start of treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Overall Survival (OS) - By Dose Level	NA months Interval 12.0 to Median is not reached because only 2 of the total 6 patients died, so the OS never fell below 0.6. The CI upper bound for the CI is also NA because the sample size is very small (n=6), and the last four patients were all censored, at 14, 14, 19 and 20 respectively.	14.00 months Interval 9.0 to The upper bound is NR because the sample size is very small.

SECONDARY outcome

Timeframe: Up to 12 months post treatment

Population: Treated patients who experienced adverse events.

Number of patients with adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, determined to be at least possibly related to treatment.

Outcome measures

Outcome measures
Measure	Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 4 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg	Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab) n=6 Participants Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - AUC of 5 mg/mL•min Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg
Worst Grade of Adverse Events Sepsis >= Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Dizziness< Grade 3	0 Participants	3 Participants
Worst Grade of Adverse Events Blood bilirubin increased< Grade 3	1 Participants	1 Participants
Worst Grade of Adverse Events Insomnia< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Paresthesia< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Anemia >= Grade 3	3 Participants	4 Participants
Worst Grade of Adverse Events Neutrophil count decreased >= Grade 3	4 Participants	4 Participants
Worst Grade of Adverse Events White blood cell decreased >= Grade 3	5 Participants	4 Participants
Worst Grade of Adverse Events Platelet count decreased >= Grade 3	1 Participants	3 Participants
Worst Grade of Adverse Events Lymphocyte count decreased >= Grade 3	2 Participants	2 Participants
Worst Grade of Adverse Events Hypomagnesemia >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Malaise >= Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Lung infection >= Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Abdominal pain >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Acute kidney injury >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Back pain >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Gastric hemorrhage >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Hypoxia >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Pain >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Pancytopenia >= Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Alanine aminotransferase increased < Grade 3	3 Participants	3 Participants
Worst Grade of Adverse Events Nausea< Grade 3	3 Participants	3 Participants
Worst Grade of Adverse Events Aspartate aminotransferase increased< Grade 3	3 Participants	2 Participants
Worst Grade of Adverse Events Fatigue< Grade 3	2 Participants	3 Participants
Worst Grade of Adverse Events Hyponatremia< Grade 3	2 Participants	3 Participants
Worst Grade of Adverse Events Alkaline phosphatase increased< Grade 3	1 Participants	2 Participants
Worst Grade of Adverse Events Anorexia< Grade 3	2 Participants	1 Participants
Worst Grade of Adverse Events Constipation< Grade 3	2 Participants	1 Participants
Worst Grade of Adverse Events Blood lactate dehydrogenase increased< Grade 3	1 Participants	1 Participants
Worst Grade of Adverse Events Chills< Grade 3	0 Participants	2 Participants
Worst Grade of Adverse Events Diarrhea< Grade 3	1 Participants	1 Participants
Worst Grade of Adverse Events Hyperglycemia< Grade 3	1 Participants	1 Participants
Worst Grade of Adverse Events Arthralgia< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Cecal hemorrhage< Grade 3	0 Participants	0 Participants
Worst Grade of Adverse Events Creatinine clearance decrease< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Dysarthria< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Dyspepsia< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Elevated Creatinine< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Fever< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Generalized muscle weakness< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Hyperphosphatemia< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Hypertension< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Hypoalbuminemia< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Hypocalcemia< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Hypophosphatemia< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Hypotension< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events INR increased< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Infusion related reaction< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Phlebitis< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Pruritus< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Rash acneiform< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Rash maculo-papular< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Restlessness< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Sinus tachycardia< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events Stomach pain< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Tinnitus< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events Vomiting< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events body aches< Grade 3	1 Participants	0 Participants
Worst Grade of Adverse Events dry heaves< Grade 3	0 Participants	1 Participants
Worst Grade of Adverse Events thrombocytopenia< Grade 3	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 30 months

Population: Did not proceed with phase II of the study; no patient tumors were tested for ATM deficiency as planned

Other events: 6 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Barbara Stadterman, MPH, MSCCR, CCRP, Clinical Research Manager

UPMC Hillman Cancer Center

Phone: 4126475554

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Dose Level -1 (Pembrolizumab, Gemcitabine, Carboplatin, M6620) n=6 participants at risk Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - 4 AUC Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg The following treatment schedule will be used for a total of two years of treatment. Pembrolizumab administration should not exceed 2 years. * Cycles 1 to 4 (first 3 months of the first year): gemcitabine on D1 and D8, carboplatin and pembrolizumab on D1, and +/- berzosertib (M6620, VX-970) on D2 and D9, every three weeks * Cycles 5 to 16 (last 9 months of the first year): pembrolizumab +/- berzosertib (M6620, VX-970) on D1, every 3 weeks * Cycles 17 to 26 (second year): pembrolizumab on D1, every 6 weeks	Dose Level 1 (Pembrolizumab, Gemcitabine, Carboplatin, M6620) n=6 participants at risk Chemotherapy-naïve patients expected to tolerate higher doses of platinum chemotherapy. Berzosertib: Given IV - 135 mg/m2 Carboplatin: Given IV - 5 AUC Gemcitabine Hydrochloride: Given IV - 800 mg/m2 Pembrolizumab: Given IV - 200 mg The following treatment schedule will be used for a total of two years of treatment. Pembrolizumab administration should not exceed 2 years. * Cycles 1 to 4 (first 3 months of the first year): gemcitabine on D1 and D8, carboplatin and pembrolizumab on D1, and +/- berzosertib (M6620, VX-970) on D2 and D9, every three weeks * Cycles 5 to 16 (last 9 months of the first year): pembrolizumab +/- berzosertib (M6620, VX-970) on D1, every 3 weeks * Cycles 17 to 26 (second year): pembrolizumab on D1, every 6 weeks
Blood and lymphatic system disorders Anemia	50.0% 3/6 • Adverse Events data were collected for 2 years, 11 months.	66.7% 4/6 • Adverse Events data were collected for 2 years, 11 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
General disorders Malaise	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
General disorders Non-cardiac chest pain	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
General disorders Pain	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Infections and infestations Lung infection	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Infections and infestations Sepsis	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Infections and infestations Urinary tract infection	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Investigations Blood bilirubin increased	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Investigations Lymphocyte count decreased	33.3% 2/6 • Adverse Events data were collected for 2 years, 11 months.	33.3% 2/6 • Adverse Events data were collected for 2 years, 11 months.
Investigations Neutrophil count decreased	66.7% 4/6 • Adverse Events data were collected for 2 years, 11 months.	66.7% 4/6 • Adverse Events data were collected for 2 years, 11 months.
Investigations Pancytopenia	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Investigations Platelet count decreased	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	50.0% 3/6 • Adverse Events data were collected for 2 years, 11 months.
Investigations White blood cell decreased	66.7% 4/6 • Adverse Events data were collected for 2 years, 11 months.	50.0% 3/6 • Adverse Events data were collected for 2 years, 11 months.
Metabolism and nutrition disorders Anorexia	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Metabolism and nutrition disorders Hyponatremia	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Nervous system disorders Dysphasia	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Nervous system disorders Seizure	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Nervous system disorders Stroke	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Nervous system disorders Transient ischemic attacks	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Renal and urinary disorders Acute kidney injury	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Vascular disorders Arterial thromboembolism	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.
Vascular disorders Hypertension	16.7% 1/6 • Adverse Events data were collected for 2 years, 11 months.	0.00% 0/6 • Adverse Events data were collected for 2 years, 11 months.