Anti-PD-1 and CapOx for the First-line Treatment of dMMR Esophagogastric Cancer (AuspiCiOus)

NCT05177133 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NL77094.018.21
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 8

Brief Summary

To investigate the effects of the combination of two chemotherapies followed by immunostimulants on the interferon gamma expression and infiltration of cytotoxic T cells in the tumour microenvironment in patients with previously untreated metastatic or locally advanced esophagogastric cancer.

Conditions

Gastric Adenocarcinoma; Esophageal Adenocarcinoma

Keywords

Advanced esophagogastric cancer; Infiltrating immune cells; IFNy expression; chemotherapy; immunotherapy; Microsatellite instability

Outcome Measures

Primary Outcomes (3)

• Effect of chemo- and immunotherapy on the interferon gamma expression signature in the tumor microenviornment

  RNA expression analysis (Nanostring) to determine changes in Interferon gamma expression signature before and during treatment

  40 months

• Effect of chemo- and immunotherapy on the immune infiltrate in the tumor microenvironment

  Flow cytometry to determine changes in immune infiltrate in the tumor before and during treatment

  40 months

• Effect of chemo- and immunotherapy on the immune infiltrate on the tumor microenvironment

  Multicolor immunohistochemstry to determine changes in immune infiltrate in the tumor before and during treatment

  40 months

Secondary Outcomes (8)

• Overall survival

  60 months

• Overall survival

  60 months

• Progression free survival (PFS)

  60 months

• Progression free survival (PFS)

  60 months

• Response rate

  60 months

Other Outcomes (8)

• Impact of cytotoxic therapy and PD-1 inhibition on the anti-tumor immune respons

  40 months

• Impact of cytotoxic therapy and PD-1 inhibition on the anti-tumor immune respons

  40 months

• Phenotype of PBMCs

  40 months

Study Arms (1)

Capecitabine, oxaliplatin and retifanlimab

EXPERIMENTAL

IV and PO Capecitabine 1000 mg/m2, oxaliplatin 130 mg/m2, every three weeks (up to 2 cycles) IV retifanlimab 500mg, every four weeks

Drug: Capecitabine; Drug: Oxaliplatin; Drug: Retifanlimab

Interventions

Capecitabine DRUG

PO Capecitabine

Also known as: Xeloda

Capecitabine, oxaliplatin and retifanlimab

Oxaliplatin DRUG

IV Oxaliplatin

Also known as: Oxaliplatin Accord

Capecitabine, oxaliplatin and retifanlimab

Retifanlimab DRUG

IV retifanlimab

Also known as: INCMGA00012

Capecitabine, oxaliplatin and retifanlimab

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent according to ICH/GCP, and national/local regulations prior to any screening procedures.
• Male or female adult patients (≥ 18 years).
• Patients with histologically confirmed diagnosis of metastatic or irresectable HER2 negative adenocarcinoma of the stomach or gastroesophageal junction (Siewert II and III); patients with HER2 positive disease are eligible when treatment with trastuzumab is contraindicated. If histology cannot be obtained, cytology is acceptable to prove metastatic disease.
• Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is allowed if other untreated lesions eligible for evaluation are present.
• Measurable disease as assessed by RECIST 1.1
• dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2 en MSH6
• Primary tumor or metastasis accessible for repeat fresh histological biopsies
• ECOG (WHO) performance status 0-2
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute Neutrophil Count (ANC) \> 1.5 x 109 /L
• Hemoglobin (Hgb) \> 5.6 mmol/L
• Platelets \> 100 x 109 /L
• Serum total bilirubin within ≤ 1.5 x ULN (upper limit of normal); or total bilirubin \< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's syndrome; biliary drainage is allowed for biliary obstruction
• Serum creatinine \< 1.5 x ULN or creatinine clearance \>30 mL/min/1.73 m2
• Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) \< 2.5x ULN within normal range or \< 5.0 x ULN if liver metastases are present

You may not qualify if:

• Severe renal impairment (CLcr ≤ 30 ml/min)
• Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment.
• Any prior anti-cancer chemotherapy, biologic or investigational therapy for metastatic or irresectable stomach or oesophageal cancer
• Disease progression within six months after completion of (neo)adjuvant chemotherapy containing a fluoropyrimidine and/or platinum compound. (Disease progression within 6 months after completion of neoadjuvant chemoradiation carboplatin AUC 2 and paclitaxel 50 mg/m2 is allowed.)
• All target lesions in a radiation field without documented disease progression.
• Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
• Past or current malignancy other than entry diagnosis interfering with prognosis of metastatic gastroesophageal cancer.
• Known uncontrollable hypersensitivity or contraindications to any of the components of retifanlimab, fluoropyrimidines, leucovorin, oxaliplatin. Patients with previous dose reductions or delays are eligible.
• Complete dihydropyrimidine dehydrogenase deficiency.
• Patient has active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy.
• Patient has known past or active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
• Signs of interstitial lung disease (ILD)
• Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study.
• Use of other investigational drugs within 30 days of enrollment.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Incyte Corporation: collaborator

Study Sites (8)

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

RECRUITING

Amsterdam UMC, location VUmc

Amsterdam, Netherlands

RECRUITING

Catharina ziekenhuis

Eindhoven, Netherlands

RECRUITING

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

NOT YET RECRUITING

LUMC

Leiden, Netherlands

NOT YET RECRUITING

Radboud UMC

Nijmegen, Netherlands

RECRUITING

Erasmus MC

Rotterdam, Netherlands

NOT YET RECRUITING

UMC Utrecht

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Microsatellite Instability

Interventions

Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Jan M Prins, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY DIRECTOR

• Hanneke WM van Laarhoven, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• Sarah Derks

  VU Medisch Centrum - Vrije Universiteit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joris Bos, MSc

CONTACT

0204440506; j.bos3@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr. H.W.M. van Laarhoven

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: January 4, 2022
• Study Start: November 5, 2021
• Primary Completion: May 1, 2025
• Study Completion (Estimated): November 4, 2029
• Last Updated: August 2, 2024

Record last verified: 2024-08

Locations

NL (8)