Trial Outcomes & Findings for M7824 (MSB0011359C) in Combination With Gemcitabine in Adults With Previously Treated Advanced Adenocarcinoma of the Pancreas (NCT NCT03451773)

Last Updated: 2021-06-16

Results Overview

Safety and tolerability of M7824 in combination with gemcitabine was assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 1 is mild; asymptomatic or mild symptoms. Grade 2 is moderate; minimal non-invasive intervention indicated.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

7 participants

Primary outcome timeframe

30 days after treatment

Results posted on

2021-06-16

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Overall Study STARTED	1	6
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Overall Study Death on study	1	5
Overall Study Death during follow-up period	0	1

Baseline Characteristics

M7824 (MSB0011359C) in Combination With Gemcitabine in Adults With Previously Treated Advanced Adenocarcinoma of the Pancreas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Age, Continuous	45.7 years STANDARD_DEVIATION 0 • n=93 Participants	55.87 years STANDARD_DEVIATION 12.54 • n=4 Participants	54.41 years STANDARD_DEVIATION 12.07 • n=27 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Region of Enrollment United States	1 participants n=93 Participants	6 participants n=4 Participants	7 participants n=27 Participants
Number of Participants with an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 ECOG 0	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Number of Participants with an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 ECOG 1	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants
Prior Therapy Chemotherapy Multiple Agents Systemic	1 Participants n=93 Participants	6 Participants n=4 Participants	7 Participants n=27 Participants
Prior Therapy Surgery	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Prior Therapy Chemotherapy Single Agent Systemic	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants
Prior Therapy Limited Radiation	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants

PRIMARY outcome

Timeframe: 30 days after treatment

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Platelet count decreased - Probably Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Alanine aminotransferase increased - Definitely Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Abdominal pain - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Alanine aminotransferase increased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Anemia - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Aspartate aminotransferase increased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Diarrhea - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Dyspnea - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Lymphocyte count decreased - Possibly Related	0 adverse events	3 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Nausea - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Neutrophil count decreased - Possibly Related	0 adverse events	4 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Platelet count decreased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Tumor pain - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 White blood cell decreased - Possibly Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Anemia - Probably Related	0 adverse events	4 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Neutrophil count decreased - Probably Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 White blood cell decreased - Probably Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Alkaline phosphatase increased - Definitely Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 2 Infusion related reaction - Definitely Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Fatigue - Possibly Related	1 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Vomiting - Possibly Related	1 adverse events	3 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Alanine aminotransferase increased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Anemia - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Anorexia - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Aspartate aminotransferase increased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Chills - Possibly Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Dehydration - Possibly Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Diarrhea - Possibly Related	0 adverse events	4 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Electrocardiogram QT corrected interval prolonged - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Fever - Possibly Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Gastrointestinal disorders - Other, Gum bleeding - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Hyperglycemia - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Lymphocyte count decreased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Nausea - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 White blood cell decreased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Bruising - Probably Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Diarrhea - Probably Related	1 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 1 Lymphocyte count decreased - Probably Related	0 adverse events	1 adverse events

PRIMARY outcome

Timeframe: 30 days after treatment

Safety and tolerability of M7824 in combination with gemcitabine was assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Anemia - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Diarrhea Possibly Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Nausea - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Neutrophil count decreased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Platelet Count Decreased - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Pleural Effusion - Possibly Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Anemia Probably Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Lymphocyte Count Decreased - Probably Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Platelet Count Decreased - Probably Related	0 adverse events	2 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 White Blood Cell Decreased - Probably Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Alanine Aminotransferase Increased - Definitely Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 3 Lipase Increased - Definitely Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 4 Neutrophil count decreased - Probably Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 4 Aspartate Aminotransferase increased - Definitely Related	0 adverse events	1 adverse events
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment Grade 5 Immune Checkpoint Inhibitor (ICI)-Induced Hepatitis - Definitely Related	0 adverse events	1 adverse events

PRIMARY outcome

Timeframe: Every 8 weeks, up to 2 years

Changes in tumor size and occurrence of metastases was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 to determine the best overall response: Complete Response (CR), Partial Response (PR), and Stable Disease (SD), whichever is recorded first. Complete Response is disappearance of all lesions, Partial Response is at least a 30% decrease in the sum of diameters of target lesions, and Stable Disease is when the sum of all target lesions does not qualify for CR, PR, or Progressive Disease (PD), defined as the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Phase II: Number of Participants With a Best Overall Response (BOR) Complete Response	0 Participants	0 Participants
Phase II: Number of Participants With a Best Overall Response (BOR) Partial Response	0 Participants	0 Participants
Phase II: Number of Participants With a Best Overall Response (BOR) Stable Disease	1 Participants	3 Participants
Phase II: Number of Participants With a Best Overall Response (BOR) Progressive Disease	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Time to resolution of adverse events, which is the time recorded until it took for the adverse event to resolve to grade 1 or less (if there is a death, it is that time), approximately 12 months.

Population: \* = death. Zero = adverse event started and resolved on the same day and/or participant died.

Duration of treatment-related AE's is defined as the time from the date treatment consent signed to end of treatment. Grade 1-4 adverse events observed in participants with pancreatic cancer assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. And Grade 4 is life-threatening.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Duration of Treatment-related Adverse Events (AEs) Pt 6 - Grade 1 Diarrhea	45 Days	—
Duration of Treatment-related Adverse Events (AEs) Pt 6 - Grade 1 Fatigue	0 Days	—
Duration of Treatment-related Adverse Events (AEs) Pt 6 - Grade 1 Vomiting	0 Days	—
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 1 Alanine aminotransferase increased	—	172 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7 - Grade 1 Alanine aminotransferase increased	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 1 Anemia	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 4* - Grade 1 Anorexia	—	27 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1* - Grade 1 Aspartate aminotransferase increased	—	173 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5* - Grade 1 Bruising	—	17 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 1 Chills first occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 1 Chills second occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade Dehydration	—	2 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Dehydration	—	301 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 1 Diarrhea	—	3 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 1 Diarrhea first occurrence	—	4 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 1 Diarrhea second occurrence	—	19 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 1 Diarrhea	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5* - Grade 1 Electrocardiogram QT corrected interval prolonged	—	31 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 1 Fatigue	—	2 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Grade 1 Fatigue	—	330 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 1 Fever	—	4 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 1 Fever	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 1 Gastrointestinal disorder - Other, specify	—	56 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1* - Grade 1 Hyperglycemia	—	151 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 1 Lymphocyte count decreased first occurrence	—	16 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Lymphocyte count decreased second occurrence	—	5 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 1 Nausea	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 1 Platelet count decreased	—	14 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3* - Grade 1 Platelet count decreased	—	50 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 1 Vomiting	—	3 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 1 Vomiting	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 1 Vomiting	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 1 White blood cell decreased	—	327 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1* - Grade 2 Abdominal pain	—	167 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 2 Alanine aminotransferase increased	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 2 Alkaline aminotransferase increased	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 2 Anemia	—	14 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 2 Anemia first occurrence	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 2 Anemia second occurrence	—	5 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 Anemia	—	14 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Grade 2 Anemia	—	327 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 Aspartate aminotransferase increased	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 2 Diarrhea	—	10 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1* - Grade 2 Dyspnea	—	176 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 1 Infusion related reaction first occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 1 - Grade 2 Infusion related reaction second occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Grade 2 Lymphocyte count decreased	—	322 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 Lymphocyte count decreased first occurrence	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3* - Grade 2 Lymphocyte count decreased second occurrence	—	32 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7 - Grade 2 Nausea	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 2 Neutrophil count decreased	—	2 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 Neutrophil count decreased first occurrence	—	14 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 Neutrophil count decreased second occurrence	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 Neutrophil count decreased third occurrence	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Grade 2 Neutrophil count decreased	—	327 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Grade 2 Platelet count decreased	—	327 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 2 Tumor pain	—	11 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade White blood cell decreased	—	2 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 White blood cell decreased first occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 White blood cell decreased second occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 2 White blood cell decreased third occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 3 Alanine aminotransferase increased	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2* - Grade 3 Anemia	—	2 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 3 Anemia	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 3 Diarrhea first occurrence	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 3 Diarrhea second occurrence	—	6 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 3 Lipase increased	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 3 Lymphocyte count decreased	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 3 Nausea	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 3 Neutrophil count decreased	—	0 Days
Duration of Treatment-related Adverse Events (AEs) Pt 2 - Grade 3 Platelet count decreased	—	3 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 3 Platelet count decreased first occurrence	—	2 Days
Duration of Treatment-related Adverse Events (AEs) Pt 5 - Grade 3 Platelet count decreased second occurrence	—	5 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 3 Pleural effusion	—	8 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 3 White blood cell decreased	—	14 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7* - Grade 4 Aspartate aminotransferase increased	—	1 Days
Duration of Treatment-related Adverse Events (AEs) Pt 3 - Grade 4 Neutrophil count decreased	—	14 Days
Duration of Treatment-related Adverse Events (AEs) Pt 7 - Grade 5 Immune system disorders - Other, Specify	—	0 Days

SECONDARY outcome

Timeframe: Every 6-12 weeks, up to 1 year

Population: This outcome measure was not done because no participants lived long enough to have confirmatory scans to confirm immune related response.

irBOR is defined as the duration of immune-related best overall response measured from the time measurement criteria are met for Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Immune related changes in tumor size and occurrence of metastases was assessed by the Modified Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Immune-related Complete Response (irCR) is complete disappearance of all lesions and no new lesions. Immune-related Partial Response (irPR) is sum of the longest diameters of target and new measurable lesions neither irCR, irPR (compared to baseline) or irPD (compared to nadir). Immune-related Progressive Disease (irPD) is appearance of new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 6 and 9 months

Participants who are alive at 6 months and 9 months after therapy.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Percentage of Evaluable Participants Alive at 6 Months and 9 Months 6 Months	NA percentage of participants Since only one participant was accrued to this cohort, no median survival times can be given. The participant progressed and died.	33.3 percentage of participants Interval 4.6 to 62.6
Percentage of Evaluable Participants Alive at 6 Months and 9 Months 9 Months	NA percentage of participants Since only one participant was accrued to this cohort, no median survival times can be given. The participant progressed and died.	16.7 percentage of participants Interval 0.8 to 51.7

SECONDARY outcome

Timeframe: 3 months

Percentage of participants who have not progressed at 3 months. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Percentage of Participants Who Have Not Progressed at 3 Months	NA percentage of participants Since only one participant was accrued to this cohort, no median survival times can be given. The participant progressed and died.	16.7 percentage of participants Interval 0.8 to 51.7

SECONDARY outcome

Timeframe: up to 1 year

Population: On participant died.

OS is the median amount of time subject survives after therapy.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Overall Median Survival	3.5 Months Interval 0.5 to 11.7	—

SECONDARY outcome

Timeframe: up to 6 months

PFS is the median amount of time subject survives without disease progression after treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=7 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Overall Progression Free Survival	1.4 Months Interval 0.5 to 5.1	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 Participants Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 Participants Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	1 Participants	6 Participants

Adverse Events

Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C)

Serious events: 6 serious events

Other events: 6 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level -1: Gemcitabine + De-escalating Dose of M7824 (MSB0011359C) n=1 participants at risk Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824 M7824:500mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy	Dose Level 0: Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C) n=6 participants at risk Gemcitabine (dose based on genetic testing results) + RP2D of M7824 M7824: 1,200mg every 2 weeks by intravenous (IV) infusion Gemcitabine: Standard (1,000 mg/m\^2) or reduced (600 mg/m\^2 for 4 doses) intravenous (IV) once a week for first 4 weeks. Then, once weekly for 3 weeks with one week rest. Gemcitabine will be discontinued after 6 months of therapy
Blood and lymphatic system disorders Anemia	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	66.7% 4/6 • Number of events 5 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
General disorders Disease progression	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Gastrointestinal disorders Duodenal hemorrhage	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Immune system disorders Immune system disorders - Other, Immune checkpoint inhibitor (ICI)- induced hepatitis	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Gastrointestinal disorders Nausea	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Investigations Platelet count decreased	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.
Vascular disorders Thromboembolic event	0.00% 0/1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 20 days for Dose Level -1, and 15 months and 20 days for Dose Level 0.

Other adverse events

Additional Information

Dr. Udo Rudloff

National Cancer Institute

Phone: 240-760-6238

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place