Gastric AdenocarcinomaPhase 2NCT07059611
Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma
A Phase 2 study testing RP2, 5-Fluorouracil and Leucovorin in people with Gastric Adenocarcinoma and Esophageal Adenocarcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- RP2, 5-Fluorouracil and Leucovorin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2027to 1 Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
- Patients with known HIV infection with an undetectable viral load and who are on a stable highly active antiviral regimen per the investigator's assessment will eligible to enroll.
- Has a psychiatric illness, substance use, or other social conditions that, in the judgment of the investigator, would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Jennifer Walsh, 609-668-0689, Jennifer.Walsh4@pennmedicine.upenn.edu
William Chapin, MD, MSCE
About this study
Official title: Phase II Study of Neoadjuvant RP2 in Combination With Preoperative Flot for Patients With Stage II or Higher, Non-metastatic Gastroesophageal Adenocarcinoma
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.
Read the detailed description
This is a single-arm, phase II study using a Simon two-stage optimal design with a 6 patient safety run-in evaluating the addition of intra-tumoral injections of RP2 to standard of care perioperative FLOT for patients with stage II or higher, non-metastatic esophageal, gastroesophageal junction (GEJ), or gastric adenocarcinoma. We hypothesize that the addition of RP2 to perioperative FLOT will be safe and will significantly improve pathologic complete response (pCR) rate compared to the historical weighted average of 12% observed with perioperative FLOT in the ESOPEC trial, MATTERHORN trial, and FLOT4 trial.
- Conditions
- Gastric Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
- Being tested
- RP2, 5-Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP2Biological
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.
5-FluorouracilCombination 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.
LeucovorinCombination product
Leucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.
OxaliplatinCombination product
Oxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.
DocetaxelCombination product
Docetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.
PegfilgrastimDrug
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.
FilgrastimDrug
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.
Surgical Resection of Primary TumorProcedure or surgery
Following 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice.
| Study group | Role | What they receive |
|---|---|---|
| RP2 and FLOT | Experimental | Not described Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Frequency of adverse events as categorized and graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in patients who received at least one dose of study treatment (Safety population).
Measured: 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
R0 resection defined as a complete resection with histologically negative margins with no macroscopic or microscopic residual tumor left behind after resection (Efficacy population).
Measured: 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)
DFS defined as time from surgical resection of esophageal, GEJ or gastric cancer to death or documented disease recurrence with censoring at the time of last patient contact if lost to follow up, or at the time of data cutoff (Efficacy population).
Measured: 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)
OS defined as the time from first study treatment to death with censoring at the time of last patient contact if lost to follow up, or at the time of data cutoff (Safety population).
Measured: Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2025
- Study start1 Apr 2027 (estimated)
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Replimune, Inc.
- Responsible party
- Sponsor
- Investigators
- William Chapin, MD, MSCE, Principal investigator, Abramson Cancer Center at the University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07059611
- Sponsor's protocol ID
- UPCC 06225
- Status last verified
- Jun 2026
- First submitted
- 8 Jul 2025
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the clinical trial publication, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant RP2 in Combination With Preoperative Flot for Patients With Stage II or Higher, Non-metastatic Gastroesophageal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT07059611
- Acronym / sponsor ID
- UPCC 06225
- Conditions
- Gastric Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Replimune, Inc.
- Study start
- 1 Apr 2027 (estimated)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2029 (estimated)
- First posted
- 11 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single-arm, phase II study using a Simon two-stage optimal design with a 6 patient safety run-in evaluating the addition of intra-tumoral injections of RP2 to standard of care perioperative FLOT for patients with stage II or higher, non-metastatic esophageal, gastroesophageal junction (GEJ), or gastric adenocarcinoma. We hypothesize that the addition of RP2 to perioperative FLOT will be safe and will significantly improve pathologic complete response (pCR) rate compared to the historical weighted average of 12% observed with perioperative FLOT in the ESOPEC trial, MATTERHORN trial, and FLOT4 trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP2Upper 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. | Biological | RP2 and FLOT |
| 5-Fluorouracil5-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. | Combination product | RP2 and FLOT |
| LeucovorinLeucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles. | Combination product | RP2 and FLOT |
| OxaliplatinOxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles. | Combination product | RP2 and FLOT |
| DocetaxelDocetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles. | Combination product | RP2 and FLOT |
| PegfilgrastimPegfilgrastim 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. | Drug | RP2 and FLOT |
| FilgrastimFilgrastim 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. | Drug | RP2 and FLOT |
| Surgical Resection of Primary TumorFollowing 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice. | Procedure or surgery | RP2 and FLOT |
Primary outcome
Pathologic complete response
Time frame: 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.
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.
4 secondary outcomes
Adverse event profile
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the clinical trial publication, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
William Chapin, MD, MSCE principal investigator
Abramson Cancer Center at the University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RP2, 5-Fluorouracil and Leucovorin in people with Gastric Adenocarcinoma and Esophageal Adenocarcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Eads, MD (215-662-3141, Jennifer.Eads@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.