Switch Maintenance in Pancreatic

NCT05419479 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: 22-141
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to test the safety and effectiveness of combining domvanalimab (AB154), zimberelimab (AB122), and APX005M with pancreatic cancer that has spread to other parts of body. This research study involves immunotherapy. Immunotherapy triggers the body's immune system to fight cancer cells. The names of the study drugs involved in this study are:

• Domvanalimab (also known as AB154)
• Zimberelimab (also known as AB122)
• APX005M

Conditions

Pancreatic Cancer; Adenocarcinoma of the Pancreas; Squamous Cell Carcinoma of Pancreas; Adenosquamous Carcinoma of the Pancreas

Keywords

Pancreatic Cancer; Adenocarcinoma of the Pancreas; Squamous Cell Carcinoma of Pancreas; Adenosquamous Carcinoma of the Pancreas

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities-Phase 1

  Toxicity assessments will be evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  28 Days

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Every 8 weeks up to 38 Months

• Disease Control Rate

  Every 8 weeks up to 38 Months

• Switch Maintenance-Progression Free Survival

  baseline up to 38 months

• Duration of Response (DoR)

  Baseline up to 38 Months

• Overall Survival

  baseline up to 38 months

Study Arms (4)

LEAD-IN: DOSE DE-ESCALATION

EXPERIMENTAL

The lead-in dose de-escalation cohort (Phase 1b) will enroll 6 patients (up to 12 patients in 2 dose levels if needed; 6 patients per DL) to receive zimberelimab, domvanalimab, and APX005M

Drug: ZIMBERELIMAB; Drug: DOMVANALIMAB; Drug: APX005M

ARM A: ZIMBERELIMAB + DOMVANALIMAB + APX005M

EXPERIMENTAL

Participants will be randomly assigned to one of two groups Arm A will receive domvanalimab, zimberelimab, and APX005M every two weeks through an infusion.

Drug: ZIMBERELIMAB; Drug: DOMVANALIMAB; Drug: APX005M

ARM B: FOLFIRI

ACTIVE COMPARATOR

Arm B will receive leucovorin, fluorouracil, and irinotecan every two weeks through an infusion

Drug: FOLFIRI

CROSSOVER: ZIMBERELIMAB + DOMVANALIMAB + APX005M

EXPERIMENTAL

Participants in Arm B (control arm) who experience disease progression (as defined by RECIST v1.1) will be given the option to crossover and receive domvanalimab + zimberelimab, + APX005M in the second-line setting, provided they meet eligibility criteria

Drug: ZIMBERELIMAB; Drug: DOMVANALIMAB; Drug: APX005M

Interventions

ZIMBERELIMAB DRUG

Via IV on two days per cycle, dosage per protocol

Also known as: AB 122

ARM A: ZIMBERELIMAB + DOMVANALIMAB + APX005M; CROSSOVER: ZIMBERELIMAB + DOMVANALIMAB + APX005M; LEAD-IN: DOSE DE-ESCALATION

DOMVANALIMAB DRUG

Via IV on two days per cycle, dosage per protocol

Also known as: AB 154

ARM A: ZIMBERELIMAB + DOMVANALIMAB + APX005M; CROSSOVER: ZIMBERELIMAB + DOMVANALIMAB + APX005M; LEAD-IN: DOSE DE-ESCALATION

APX005M DRUG

Via IV on two days per cycle, dosage per protocol

Also known as: CD40

ARM A: ZIMBERELIMAB + DOMVANALIMAB + APX005M; CROSSOVER: ZIMBERELIMAB + DOMVANALIMAB + APX005M; LEAD-IN: DOSE DE-ESCALATION

FOLFIRI DRUG

every two weeks through an infusion at a dose determined by physician

ARM B: FOLFIRI

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed pancreatic cancer (adenocarcinoma, squamous, or adenosquamous histologies) that is metastatic and for which standard curative or palliative measures do not exist or are no longer effective. Locally advanced patients are not eligible.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
• Participants must have received 8-12 cycles (4-6 months) of first-line FOLFIRINOX or modified FOLFIRINOX with stable disease or better.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of domvanalimab + zimberelimab + APX005M in participants \<18 years of age, children are excluded from this study.
• ECOG performance status ≤1
• Participants must have adequate organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except in patients with documented Gilbert's syndrome, who must have a total bilirubin ≤ 3 x ULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x institution's upper limit of normal (ULN) for patients with no concurrent liver metastases, OR ≤ 5.0 x institution's ULN for patients with concurrent liver metastases creatinine OR glomerular filtration rate (GFR) creatinine ≤ 2 x ULN OR GFR measured by calculated creatinine clearance (CrCl) \> 45 mL/min. CrCl can be calculated using the Cockroft-Gault method.
• Hemoglobin (Hgb) \>9.0 g/dL
• Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. If a participant has brain or meningeal metastases, the participant must meet the following criteria:
• Have no evidence of progression by neurologic symptoms or sign for at least 4 weeks prior to the first dose.
• Metastatic brain lesions do not require immediate intervention.

You may not qualify if:

• Patients who have evidence of disease progression on FOLFIRINOX.
• Participants who have had cytotoxic chemotherapy, radiotherapy, within 2 weeks prior to the first dose of study medication or those who have not recovered to ≤ CTCAE Grade 1 or baseline from adverse events due to agents administered more than 2 weeks earlier. Exceptions include alopecia of any grade and Grade ≤ 2 peripheral neuropathy.
• Participants who have received any other investigational agents for pancreatic cancer.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, or allergic reactions attributed to compounds of similar chemical or biologic composition to domvanalimab, zimberelimab, APX005M, or other agents used in study.
• Prior treatment with any of the protocol-specified study treatments, with the exception of chemotherapy.
• Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies (including anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-TIGIT, and CD40 agonist therapeutic antibodies)
• Patients with endocrine or acinar pancreatic carcinoma are not eligible for the study.
• Known dihydropyrimidine dehydrogenase deficiency.
• Patients who are enrolling after achieving at least stable disease on FOLFIRINOX are not eligible if they have a germline BRCA1 or BRCA2 mutation(s).
• Participants who have undergone major surgery 28 days prior to initiating protocol therapy. Participants must have sufficiently recovered from adverse events caused by the procedure as judged by the treating investigator. Placement of central venous access catheter (e.g., port or similar) is not considered a major surgical procedure.
• Participants must not have a history of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV), except for the following:
• Participants with anti-HepB core antibody but with undetectable HepB virus deoxyribonucleic acid (DNA) and negative for HepB surface antigen
• Participants with resolved or treated hepatitis C virus (HCV) (i.e., HCV antibody positive but undetectable HCV RNA)
• Participants must not have a history of primary immunodeficiency.
• Active autoimmune disease, history of autoimmune disease, or concurrent administration of immune suppressive medications. Participants must not have a known or suspected history of an autoimmune disorder within 3 years of the first dose of investigational agent, including but not limited to: systemic lupus erythematosus, scleroderma, inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, sarcoidosis, or autoimmune hepatitis. Exceptions include participants with Type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders such as alopecia or vitiligo, not requiring systemic therapy, resolved childhood asthma/atopy, or conditions not expected to recur in the absence of an external trigger are eligible. Patients with a history of Hashimoto syndrome within 3 years of the first dose of investigational agent, which resolved to hypothyroidism alone.

Sponsors & Collaborators

• James Cleary, MD, PhD: lead
• Arcus Biosciences, Inc.: collaborator
• Lustgarten Foundation: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

zimberelimab; sotigalimab; IFL protocol

Condition Hierarchy (Ancestors)

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

Study Officials

• James Cleary, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 15, 2022
• Study Start: November 30, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)