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NCT04327986

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

Terminated Phase 1, PHASE2 Results posted Last updated 18 May 2022
What this trial tests

Phase 1, PHASE2 trial testing M7824 in Histologically or Cytologically Confirmed Pancreatic Cancer in 3 participants. Terminated before completion.

Timeline
15 June 2021
Primary endpoint
18 January 2022
3 February 2022

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment3
Start date15 June 2021
Primary completion18 January 2022
Estimated completion3 February 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Histologically or Cytologically Confirmed Pancreatic Cancer or Unresectable or Borderline Resectable Pancreatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) for All Participants Secondary · Time interval from start to treatment to disease progression, an average of 4 months.

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.

GroupValue95% CI
Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation42.3 – 5.9
Progression-free Survival (PFS) for Participants Who Did Not Undergo Surgical Resection Secondary · time interval from start of treatment to documented evidence of disease progression

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.

GroupValue95% CI
Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation42.3 – 5.9
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Secondary · 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

GroupValue95% CI
Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation3
Number of Participants With a Dose-limiting Toxicity (DLT) Secondary · 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.

GroupValue95% CI
Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation1

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 4 months and 13 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 Phase 1A/Arm 1A Dose Level 0 De-Escalation
Serious: 1/3 (33%)
Deaths: 1/3

Serious adverse events (2 terms)

ReactionSystemCohort 1 Phase 1A/Arm 1A D…
AnemiaBlood and lymphatic system disorders
Vascular disorders - Other, gastrointestinal hemorrhageVascular disorders
Other adverse events (18 terms — click to expand)

ReactionSystemCohort 1 Phase 1A/Arm 1A D…
Infusion related reactionInjury, poisoning and procedural complications
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
Blood and lymphatic system disorders - Other, elevated white blood cellsBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
DysgeusiaNervous system disorders
FatigueGeneral disorders
FeverGeneral disorders
HypotensionVascular disorders
MalaiseGeneral disorders
MyalgiaMusculoskeletal and connective tissue disorders
Oral hemorrhageGastrointestinal disorders
Peripheral sensory neuropathyNervous system disorders
Productive coughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, rashSkin and subcutaneous tissue disorders
ThrushInfections and infestations

Most-reported serious reactions: Anemia, Vascular disorders - Other, gastrointestinal hemorrhage.

Data from ClinicalTrials.gov NCT04327986 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting TGF-β signal transduction for fibrosis and cancer therapy.
    Peng D, Fu M, Wang M, Wei Y, et al · · 2022 · cited 752× · PMID 35461253 · DOI 10.1186/s12943-022-01569-x
  2. Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
    Naimi A, Mohammed RN, Raji A, Chupradit S, et al · · 2022 · cited 350× · PMID 35392976 · DOI 10.1186/s12964-022-00854-y
  3. Targeting TGFβ signal transduction for cancer therapy.
    Liu S, Ren J, Ten Dijke P. · · 2021 · cited 302× · PMID 33414388 · DOI 10.1038/s41392-020-00436-9
  4. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  5. Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
    Vafaei S, Zekiy AO, Khanamir RA, Zaman BA, et al · · 2022 · cited 190× · PMID 34980128 · DOI 10.1186/s12935-021-02407-8
  6. Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer.
    Geng X, Chen H, Zhao L, Hu J, et al · · 2021 · cited 146× · PMID 34336821 · DOI 10.3389/fcell.2021.655152
  7. Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma.
    Zhang T, Ren Y, Yang P, Wang J, et al · · 2022 · cited 142× · PMID 36284087 · DOI 10.1038/s41419-022-05351-1
  8. Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.
    Wang Y, Johnson KCC, Gatti-Mays ME, Li Z. · · 2022 · cited 103× · PMID 36031601 · DOI 10.1186/s13045-022-01335-y

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04327986.

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