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

NCT04327986 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 20007420-C-0074
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Fewer than 10 percent of people with pancreas cancer can have surgery. Surgery gives the best outcome. Radiation therapy is usually used to make surgery possible. But it does not work for most people. Adding immunotherapy might help. Objective: To find a safe combined dose of Bintrafusp Alfa (M7824), NHS-IL12 (M9241, and radiation and to see if it causes pancreas cancer tumors to shrink. Eligibility: People ages 18 and older who have pancreas cancer and cannot have curative surgery Design: Participants will be screened under protocol 01-C-0129 with: Medical history Physical exam Heart, urine, and blood tests Scans. For this, participants will lie in a machine that takes pictures of the body. They may receive a contrast agent by vein. Possible tumor biopsy Participants will take the study drugs either alone or with radiation. They will get M7824 by vein every 2 weeks. They will get M9241 injected under the skin every 4 weeks. Participants who get radiation will get it 5 days in a row the first month. Participants will have visits every 2 weeks. They will repeat screening tests. If participants tumors shrink, they will have surgery. If their whole tumor is removed, they will stop treatment. They will otherwise continue treatment as long as they can tolerate it and it is helping them. Participants will have visits 1 week and 1 month after they stop treatment. Then they will be contacted by phone or email for life. If they stop treatment for a reason other than their disease getting worse, they will have scans every 12 weeks.

Conditions

Histologically or Cytologically Confirmed Pancreatic Cancer; Unresectable or Borderline Resectable Pancreatic Cancer; Pancreatic Neoplasms; Pancreatic Cancer; Metastatic Pancreatic Cancer

Keywords

Neoadjuvant therapy; Anti-Tumor Activity; Synergistic Anti-cancer Activity; Combining Immunotherapy and Radiation Therapy

Outcome Measures

Primary Outcomes (3)

• Recommended Phase 2 Dose (RP2D) of NHS-IL12 (M9241) Given With Bintrafusp Alfa (M7824) in Combination With Stereotactic Body Radiation Therapy (SBRT) as Neoadjuvant / Perioperative Treatment in Participants With Pancreas Cancer

  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.

  First 28 days of treatment

• Number of Participants With ≥Grade 3 Toxicities Possibly, Probably, or Definitely Related to Treatment of Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) in Combination With Stereotactic Body Radiation Therapy (SBRT)

  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.

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

• Best Overall Response (BOR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) of Bintrafusp Alfa (M7824) & NHS-IL12 (M9241) in Combination With Stereotactic Body Radiation Therapy in Participants With Locally Advanced Pancreas Cancer

  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.

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

Secondary Outcomes (6)

• Overall Survival (OS) in Participants After Completion of Radiation Therapy (RT) in Combination With NHS-IL12 (M9241) and Bintrafusp Alfa (M7824)

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

• Progression-free Survival (PFS) for All Participants

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

• Progression-free Survival (PFS) for Participants Who Did Not Undergo Surgical Resection

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

• Fraction of Participants With Locally Advanced, Non-metastatic Pancreas Cancer (LAPC) Who Are Able to Undergo Surgical Resection After Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) in Combination With Stereotactic Body Radiation Therapy (SBRT) Treatment

  At time of surgical resection

• Time-to-recurrence of the Disease For Participants Who Underwent Surgical Resection After Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) in Combination With Stereotactic Body Radiation Therapy (SBRT) Treatment

  At disease recurrence after surgical resection

Other Outcomes (2)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

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

• Number of Participants With a Dose-limiting Toxicity (DLT)

  First 28 days of treatment

Study Arms (3)

Cohort 1 Phase 1A/Arm 1A

EXPERIMENTAL

De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824)

Drug: M7824; Drug: M9241

Cohort 2 Phase 1B/Arm 1B

EXPERIMENTAL

De-escalating doses of NHS-IL12 (M9241) in combination with bintrafusp alfa (M7824) and stereotactic body radiotherapy (SBRT)

Drug: M7824; Drug: M9241; Radiation: SBRT

Phase II Cohort 3/Arm 2

EXPERIMENTAL

Recommended phase 2 dose (RP2D) of bintrafusp alfa (M7824) and NHS-IL12 (M9241) in combination with stereotactic body radiotherapy (SBRT)

Drug: M7824; Drug: M9241; Radiation: SBRT

Interventions

M7824 DRUG

Intravenous (IV) on Days 1 and 15 of every cycle

Also known as: bintrafusp alfa

Cohort 1 Phase 1A/Arm 1A; Cohort 2 Phase 1B/Arm 1B; Phase II Cohort 3/Arm 2

M9241 DRUG

Subcutaneous injection on Day 1 of every cycle

Also known as: NHS-IL12

Cohort 1 Phase 1A/Arm 1A; Cohort 2 Phase 1B/Arm 1B; Phase II Cohort 3/Arm 2

SBRT RADIATION

Radiation therapy will be starting on Day 17 (+5 days) of Cycle 1 and continue for 5 consecutive business days.

Also known as: Stereotactic body radiotherapy

Cohort 2 Phase 1B/Arm 1B; Phase II Cohort 3/Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven pancreatic adenocarcinoma (subjects with endocrine or acinar pancreatic carcinoma are not eligible).
• Patients must have stage III or IV pancreatic cancer (Cohort 1) or locally advanced pancreas cancer (LAPC), either borderline resectable pancreas cancer or locally advanced, unresectable pancreas cancer (Cohorts 2 and 3).
• Patient must be eligible to undergo stereotactic body radiation therapy (SBRT) and have fiducial markers placed (any metal biliary stents are an acceptable alternative) (Cohorts 2-3).
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of bintrafusp alfa (M7824) and NHS-IL12 (M9241) in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Adequate hematological function defined by:
• white blood cell (WBC) count greater than or equal to 3 times 10\^9/L
• with absolute neutrophil count (ANC) greater than or equal to 1.0 times 10\^9/L,
• lymphocyte count greater than or equal to 0.5 times 10\^9/L,
• platelet count greater than or equal to 100 times 10\^9/L, and
• Hemoglobin (Hgb) greater than or equal to 9 g/dL (in absence of blood transfusion)
• Adequate renal function defined by:
• Creatinine OR Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl)
• \< 1.75 x institution upper limit of normal OR

You may not qualify if:

• Treatment with any investigational agent within 28 days before treatment initiation.
• Prior therapy with any antibody / drug targeting T cell coregulatory proteins (immune checkpoints) such as anti-Programmed cell death protein 1 (PD-1), anti-Programmed death-ligand 1 (PD-L1), or anti-cluster of differentiation 152 (CTLA-4) antibody.
• Anticancer treatment within designated period before treatment initiation including:
• major surgical procedure (such as laparotomy) within 28 days
• minor surgical procedure (such as biliary stenting) within 7 days
• chemotherapy with published half-life known to be 72 hours within 7 days
• chemotherapy with unpublished or half-life greater than 72 hours within 28 days
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, except of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant)
• Significant acute or chronic infections including tuberculosis (history of exposure or history of positive tuberculosis test; plus, presence of clinical symptoms, physical or radiographic findings)
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with the exceptions:
• diabetes type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;
• subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to 10 mg of prednisone or equivalent per day;
• administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation.
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to 3 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0, any history of anaphylaxis or history of uncontrolled asthma.
• Known alcohol or drug abuse.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

bintrafusp alfa protein, human; NHS-IL12 immunocytokine; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Udo Rudloff
• Organization: National Cancer Institute

udo.rudloff@nih.gov

240-760-6238

Study Officials

• Udo Rudloff, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2020
• First Posted: March 31, 2020
• Study Start: June 15, 2021
• Primary Completion: January 18, 2022
• Study Completion: February 3, 2022
• Last Updated: May 18, 2022
• Results First Posted: May 18, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Genomic data are available once genomic data are uploaded per protocol genomic data sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)