Trial Outcomes & Findings for Immune Checkpoint Inhibitor M7824 and the Immunocytokine M9241 in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Advanced Pancreas Cancer (NCT NCT04327986)

Last Updated: 2022-05-18

Results Overview

The recommended phase 2 dose (RP2D) is the dose level of M9241 in combination with M7824 at which ≤1 of 6 individuals experienced a dose limiting toxicity (DLT) during the first cycle (28 days) of combinational treatment with M9241 and M7824. A DLT is any Grade ≥ 3 adverse events occurring during the first 28 days of treatment except adverse events unrelated, or unlikely related to study agents and probably or definitely related to other causes.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

3 participants

Primary outcome timeframe

First 28 days of treatment

Results posted on

2022-05-18

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks	Cohort 2 Phase 1B Arm 1B No participants were enrolled on Cohort 2 Phase 1B Arm 1B. The study never progressed beyond stage 1A.	Phase II Cohort 3 Arm 2 No participants were enrolled on Phase II Cohort 3 Arm 2. The study never progressed beyond stage 1A.
Overall Study STARTED	3	0	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks	Cohort 2 Phase 1B Arm 1B No participants were enrolled on Cohort 2 Phase 1B Arm 1B. The study never progressed beyond stage 1A.	Phase II Cohort 3 Arm 2 No participants were enrolled on Phase II Cohort 3 Arm 2. The study never progressed beyond stage 1A.
Overall Study Physician Decision	2	0	0
Overall Study Death	1	0	0

Baseline Characteristics

Immune Checkpoint Inhibitor M7824 and the Immunocytokine M9241 in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Advanced Pancreas Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=3 Participants De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	61.3 years STANDARD_DEVIATION 10.43 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: First 28 days of treatment

Population: Data was not collected because the study never got beyond phase 1A and was terminated, thus the RP2D was not found.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 4 months and 13 days.

Population: No data were collected because no participants received SBRT WITH M7824 and M9241.

Adverse events were assessed using the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse events.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: time measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented

Population: No data were collected because no participants received SBRT WITH M7824 and M9241.

Best overall response is measured from the time measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented using the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in target lesions. In the case of a PR or CR a confirmatory computed tomography or magnetic resonance imaging scan should be done no sooner than 4 weeks. Progressive Disease (PD) is at least a 20% increase in target lesions and/or the appearance of new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: date of on-study to the date of death from any cause or last follow

Population: Data were not collected because no participants received RT.

Overall survival is defined as date of on-study to the date of death from any cause or last follow up.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time interval from start to treatment to disease progression, an average of 4 months.

Population: 2/3 participants were evaluable because one participant did not make it to his first restaging scan.

Progression free survival is defined as the time interval from start of treatment to documented evidence of disease progression. Progression was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in target lesions and/or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=2 Participants De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Progression-free Survival (PFS) for All Participants	4 Months Interval 2.3 to 5.9

SECONDARY outcome

Timeframe: time interval from start of treatment to documented evidence of disease progression

Population: 2/3 participants were evaluable because one participant did not make it to his first restaging scan.

Outcome measures

Outcome measures
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=2 Participants De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Progression-free Survival (PFS) for Participants Who Did Not Undergo Surgical Resection	4 Months Interval 2.3 to 5.9

SECONDARY outcome

Timeframe: At time of surgical resection

Population: No data were collected because no participants had M7824 and M9241 WITH SBRT.

Fraction of participants with LAPC who are able to undergo surgical resection after M7824, M9241 and SBRT.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At disease recurrence after surgical resection

Population: No participants made it to surgical resection nor had SBRT.

Time-to-recurrence of disease is defined as time from surgical resection to disease recurrence (expressed in months).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At time of surgical resection

Population: No data were collected because no participants received M7824, M9241 WITH SBRT.

Complete Pathological Response is defined as the fraction of participants who had a complete pathologic response of all participants who underwent surgery. Complete pathological response was measured using the Response Evaluation Criteria in Solid Tumors and is defined as

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 4 months and 13 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 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	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=3 Participants De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First 28 days of treatment

A DLT is any Grade ≥ 3 adverse events occurring during the first 28 days of treatment except adverse events unrelated, or unlikely related to study agents and probably or definitely related to other causes.

Outcome measures

Outcome measures
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=3 Participants De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Number of Participants With a Dose-limiting Toxicity (DLT)	1 Participants

Adverse Events

Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=3 participants at risk De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Vascular disorders Vascular disorders - Other, gastrointestinal hemorrhage	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 13 days.

Other adverse events

Other adverse events
Measure	Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation n=3 participants at risk De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) M7824: Intravenous (IV) on Days 1 and 15 of every cycle M9241: Subcutaneous injection on Day 1 of every cycle M7824, 1200mg intravenous every 2 weeks; M9241, 16.8g/kg, subcutaneously, every 4 weeks
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, elevated white blood cells	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Nervous system disorders Dysgeusia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
General disorders Fatigue	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
General disorders Fever	33.3% 1/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Injury, poisoning and procedural complications Infusion related reaction	66.7% 2/3 • Number of events 4 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
General disorders Malaise	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Gastrointestinal disorders Oral hemorrhage	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Respiratory, thoracic and mediastinal disorders Productive cough	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, rash	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.
Infections and infestations Thrush	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 13 days.

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