NCT06048484

Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma

A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating Neoadjuvant Therapy Targeting the Adenosine Immunosuppressive Pathway in Combination With Immune Checkpoint Blockade and Radiation Therapy in Patients With Advanced PANCreatic Ductal Adenocarcinoma Who Are Candidates for Surgical Resection

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Gulam Manji · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). The study hopes that these drugs will work in concert with radiation therapy to kill cancer cells. The specific goal of this study is to ensure that treatment with zimberelimab and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.

Detailed description

The overall objective of this study is to combine standard radiation therapy with drugs that stimulate the body's immune system against cancer cells (by targeting the protein programmed cell death (PD-1), while adding drugs which also target the pathway that the tumor uses to evade the immune system (the CD73 and A2a/b pathways).The main goal of this study is to find out if study treatment with zimberelimab (an antibody which binds the protein PD-1) and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor. The study is divided into two parts (Stage 1 and Stage 2). In Stage 1 participants will undergo 5 days of SBRT and receive zimberelimab, quemliclustat and etrumadenant (Arm A) for 7 weeks before surgery. If this combination is considered safe, the study will proceed to Stage 2. In Stage 2, participants will be randomized into one of three different treatment arms (B - D). All participants will undergo SBRT and will receive either Zimberelimab alone (Arm B), a combination of zimberelimab with quemliclustat (Arm C), or will receive combination of zimberelimab, quemliclustat and etrumadenant (Arm D) for 7 weeks prior to surgery.

Conditions

• Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
RADIATION	Stereotactic body radiotherapy (SBRT)	SBRT 40 gray (Gy) over 5 fractions
DRUG	Zimberelimab	240 mg intravenously (IV)
DRUG	Quemliclustat	100 mg IV
DRUG	Etrumadenant	150 mg orally
DRUG	Modified FOLFIRINOX	* Oxaliplatin 85 mg per square meter IV * Irinotecan 150 mg per square meter IV * Leucovorin 400 mg per square meter IV * Fluorouracil 2400 mg per square meter IV * Pegfilgrastim injector kit (6mg subcutaneous)

Timeline

• Start date: 2024-05-10
• Primary completion: 2027-04-01
• Completion: 2027-04-01
• First posted: 2023-09-21
• Last updated: 2026-02-27

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study