Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma

NCT07059611 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UPCC 06225
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The research study is being conducted to study whether performing injections of a new treatment, called RP2, directly into stomach and esophagus tumors along with standard chemotherapy (called FLOT) is safe and whether it does a better job of killing cancer before surgery compared to chemotherapy alone.

Conditions

Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response

  Pathologic complete response defined as the absence of residual invasive cancer on histologic examination of the resected esophageal, GEJ, or gastric adenocarcinoma specimen and all sampled regional lymph nodes. This will be assessed in the efficacy population who received at least three intra-tumoral injections of RP2 and underwent subsequent surgical resection.

  Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.

Secondary Outcomes (4)

• Adverse event profile

  The adverse event reporting period first RP2 intratumoral injection until 30 days post-surgical resection or 56 days after the last administration of RP2 (if no resection or or consent withdrawal).

• R0 resection rate

  Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.

• Disease-free Survival (DFS)

  Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.

• Overall Survival (OS)

  Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.

Other Outcomes (1)

• Exploratory

  Blood plus/minus tissue samples will be collected during the preoperative FLOT and RP2 injection, at surgical resection, and the first cycle of post-operative FLOT. These collections will occur within the first 6-8 months on the study.

Study Arms (1)

RP2 and FLOT

EXPERIMENTAL

Biological: RP2; Combination Product: 5-Fluorouracil; Combination Product: Leucovorin; Combination Product: Oxaliplatin; Combination Product: Docetaxel; Drug: Pegfilgrastim; Drug: Filgrastim; Procedure: Surgical Resection of Primary Tumor

Interventions

RP2 BIOLOGICAL

Upper endoscopy with RP2 intra-tumoral injection of 1 x 10(6) plaque forming units (PFU)/mL for first intra-tumoral injection, up to 10mL of 1x107 PFU/mL of RP2 for subsequent intra-tumoral injections. Injection will occur within 4 days prior of each cycle FLOT.

RP2 and FLOT

5-Fluorouracil COMBINATION_PRODUCT

5-Fluorouracil as part of the FLOT regimen 2,600mg/m2 intravenous infusion over 24 hours on day 1 of each 14-day cycle for 4 cycles.

RP2 and FLOT

Leucovorin COMBINATION_PRODUCT

Leucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

RP2 and FLOT

Oxaliplatin COMBINATION_PRODUCT

Oxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

RP2 and FLOT

Docetaxel COMBINATION_PRODUCT

Docetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

RP2 and FLOT

Pegfilgrastim DRUG

Pegfilgrastim or Filgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

RP2 and FLOT

Filgrastim DRUG

Filgrastim or Pegfilgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

RP2 and FLOT

Surgical Resection of Primary Tumor PROCEDURE

Following 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice.

RP2 and FLOT

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed and clinically staged T2 or higher or node positive, non-metastatic esophageal, gastroesophageal junction, or gastric adenocarcinoma.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform the appropriate surgical procedure based on patient's primary tumor site.
• Patients must have normal organ and bone marrow function, as defined below, less than or equal to 14 days prior to the initiation of study therapy:
• Absolute neutrophil count (ANC) ≥ 1,500/microliter
• Platelets ≥100,000/microliter
• Total bilirubin ≤ the institutional upper limit of normal (ULN).
• AST and ALT ≤ 2.5 times the institutional ULN
• Serum creatinine ≤ 1.5 times the institutional ULN
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• Has received prior chemotherapy, radiation therapy, or immunotherapy (anti-programmed cell death protein-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) for the current malignancy.
• Per the investigator, has contraindications to receiving chemotherapy with FLOT.
• Per the sub-investigator (gastroenterologist) responsible for intra-tumoral injections or the investigator, patient has contraindications to repeated upper endoscopy for intra-tumoral injections. These could include medical conditions that would, per the judgment of the sub-investigator or investigator, inappropriately increase the risk of upper endoscopy.
• Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on warfarin with a target international normalized ratio (INR) ≥ 2.5 that cannot be temporarily reversed to INR ≤ 1.7.
• Active significant herpetic infections or prior complications of Herpes simplex virus-1 (HSV-1) infection (e.g., herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or intravenous \[IV\]) antivirals with known antiherpetic activity (e.g., acyclovir). Note: Patients with sporadic cold sores may be enrolled as long as no active cold sores are present at the time of first dose of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Available COVID-19 vaccines do not contain live virus and are allowed.
• Has a condition requiring systemic treatment with corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of first study treatment administration.
• Inhaled or topical steroids and adrenal replacement doses ≤ 10mg/day of prednisone equivalents are permitted.
• Prior organ transplantation including allogeneic stem-cell transplantation.
• Has a previous or concurrent malignancy. Exceptions include:
• Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ OR
• Prior malignancy has been completely excised or removed and patient has been continuously disease free for \> 5-years
• Has a positive test result for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection with hepatitis B or hepatitis C. Testing will be performed as part of screening on the study.
• Patients with a known history of hepatitis B or hepatitis C that have been effectively treated (with negative HBsAg and HCV RNA) will be eligible for enrollment on this criterion.
• Has a known history of human immunodeficiency virus (HIV) with detectable viral load. HIV testing will not be performed as part of screening for the study.

Sponsors & Collaborators

• Replimune Inc.: collaborator
• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center at the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; pegfilgrastim; Filgrastim

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• William Chapin, MD, MSCE

  Abramson Cancer Center at the University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Eads, MD

CONTACT

215-662-3141; Jennifer.Eads@pennmedicine.upenn.edu

William Chapin, MD, MSCE

CONTACT

215-662-7606; William.Chapin@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: July 11, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 3 months following clinical trial publication. No end date.
• Access Criteria: To achieve aims in an approved proposal. Proposals should be directed to corresponding author on the clinical trial publication.

Locations

US (1)