AGEN1423 and Botensilimab w/ or w/o Chemo in PDAC

NCT05632328 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-213
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to asses the safety and efficacy of the combination of AGEN1423 and Botensilimab with or without chemotherapies, gemcitabine and nab-paclitaxel, for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC) which has progressed after at least one previous line of cancer therapy. The names of the study drugs involved in this study are:

• AGEN1423
• Botensilimab Participants will receive study treatment for about 2 years and will be followed for 1 year after.

Conditions

Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer; Advanced Pancreatic Ductal Adenocarcinoma

Keywords

Advanced Pancreatic Ductal Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer; Chemotherapy; Immunotherapy; AGEN1423; Botensilimab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The objective response rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria, using the modified intent-to-treat (mITT) analysis set

  Every 8 weeks until EOT, for up to 2 years.

Secondary Outcomes (5)

• Disease Control Rate

  Every 8 weeks from first day of treatment until EOT for both cohorts up to 2 years.

• Median Duration of Overall Response (DOR)

  Up to approximately 2 years

• Median Overall Survival (OS)

  Up to 2 Years

• Median Progression-free Survival

  Every 8 weeks from first day of treatment until EOT for both cohorts up to 4 Years

• Grade 3-5 Treatment-related Toxicity Rate

  For Cohort 1 AE evaluated on Cycle 1 days 1 and 8, and Day 1 of each subsequent cycle (each cycle is 14 days). For Cohort 2 AE evaluated on Cycle 1 days 1, 8 and 15 of each cycle (each cycle is 28 days).

Study Arms (2)

COHORT 1: AGEN1423 Plus Botensilimab

EXPERIMENTAL

Treatment is AGEN1423 plus Botensilimab for 4 cycles (8 weeks) followed by Botensilimab alone for up to 2 years. AGEN1423 will be administered in a total of 4 doses. Botensilimab will be administered every 2 weeks.

Drug: AGEN1423; Drug: Botensilimab

COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy

EXPERIMENTAL

Treatment is AGEN1423 plus Botensilimab in combination with gemcitabine and nab-paclitaxel for 2 cycles (8 weeks) followed by Botensilimab in combination with gemcitabine and nab-paclitaxel for up to 2 years. AGEN1423 will be administered in a total of 4 doses. Botensilimab will be administered once every 2 weeks.

Drug: AGEN1423; Drug: Botensilimab; Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

AGEN1423 DRUG

via IV, dosage per protocol, once every 2 weeks for up to 8 weeks

Also known as: Anti-CD73-TGFβ-Trap Bifunctional Antibody

COHORT 1: AGEN1423 Plus Botensilimab; COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy

Botensilimab DRUG

via IV, dosage per protocol, once evert 2 weeks, up to 2 years

COHORT 1: AGEN1423 Plus Botensilimab; COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy

Gemcitabine DRUG

per standard care

Also known as: Gemzar

COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy

Nab-paclitaxel DRUG

per standard care

Also known as: Abraxane

COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy

Eligibility Criteria

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

You may qualify if:

• year and older
• Ability to understand and willingness to sign a written informed consent prior to entering the study.
• Histologically or cytologically confirmed (either previously or newly biopsied) metastatic or locally advanced unresectable pancreatic adenocarcinoma, including intraductal papillary mucinous neoplasm.
• Have measurable disease (≥ 1 measurable lesion) based on RECIST v1.1 as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Previous treatment lines
• Cohort 1: Have documented objective radiographic progression on or after stopping treatment with first-line or further therapy, i.e. chemotherapy and or radiotherapy. If subjects received prior neoadjuvant or adjuvant chemotherapy and progressed within 3 months of the last dose, then this should be considered as a prior line of systemic therapy.
• Cohort 2: Have documented objective radiographic progression on or after stopping treatment with first-line, fluorouracil-based chemotherapy.
• For Cohort 1, willing to submit an evaluable fresh tumor tissue sample, unless tumor is considered inaccessible, or biopsy is otherwise considered not in the subject's best interest.
• Complete resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia and peripheral neuropathy). If the subject received major surgery or radiation therapy of \> 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
• ECOG status ≤1
• Life expectancy of at least 3 months
• Participants must have adequate organ and marrow function as defined below. All laboratory assessments should be performed within 10 days of treatment initiation
• Hematological:
• Hemoglobin ≥ 9g/dL (without transfusion within 7 days of assessment)
• Leukocytes ≥3,000/µL

You may not qualify if:

• Has a pancreatic tumor other than adenocarcinoma, including: adenosquamous, acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma, Vater and periampullary duodenal or common bile duct malignancies.
• Subjects with a bowel obstruction.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has an active infection requiring systemic therapy or has an uncontrolled infection.
• Has an underlying medical condition that would preclude study participation.
• Has a disease that is suitable for therapy administered with curative intent.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AE due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at Baseline) from AE due to a previously administered agent (Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study. If subject underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy)
• An active autoimmune disease that has required systemic treatment in the 2 years preceding the study (i.e., with the use of disease-modifying agents, corticosteroids or immuno-suppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has a history of interstitial lung disease.
• O2 saturation \< 92% (on room air).
• Has unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, and current congestive heart failure New York Heart Association Class III or higher. For Cohort 2: has ventricular arrhythmias, hypertensive urgency, or severe arterial thromboembolic events less than 6 months prior to study initiation.

Sponsors & Collaborators

• Bruno Bockorny: lead
• Agenus Inc.: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Bruno Bockorny, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 30, 2022
• Study Start: August 8, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (1)