Nivolumab +/- Relatlimab Prior to Chemoradiation With II/III Gastro/Esophageal Cancer

NCT03044613 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J1714IRB00122689
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

Anti-PD-1 (nivolumab) or Anti-PD1/Anti LAG-3- (relaltimab) administration in the pre-operative setting with chemoradiation will be safe and feasible in patients with resectable distal esophageal/gastroesophageal junction cancer and will change cellular and molecular characteristics of the tumor microenvironment that will improve survival.

Conditions

Gastric Cancer; Esophageal Cancer; GastroEsophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  To investigate the safety of induction nivolumab or nivolumab/relatlimab administration prior to concurrent chemoradiation and nivolumab or nivolumab/relatlimab in subjects with resectable stage II/III gastro-esophageal junction cancer.

  100 days

Secondary Outcomes (6)

• Feasibility is assessed through the proportion of eligible patients who proceed to surgery without substantial delay (more than 60 days) due to treatment-related reasons

  12 weeks

• Pathological Complete Response Rate

  2 years

• Approximate quantitation of infused nivolumab bound to PD-1 receptors on the surface of T cells in the peripheral blood and within the resected tumor and lymph node specimens

  2 years

• Changes in Expression of Selected Immune Markers

  2 years

• Overall Survival

  2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Nivolumab 240mg administered IV over 30 minutes every 2 weeks for 2 cycles and then standard of care chemoradiation (weekly carboplatin/paclitaxel and concurrent radiation

Drug: Nivolumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation

Arm B

EXPERIMENTAL

Nivolumab 240mg administered IV over 30 minutes followed by relatlimab 80mg administered IV over 60 minutes on Day 1 every 2 weeks for 2 cycles and then standard of care chemoradiation (weekly carboplatin/paclitaxel and concurrent radiation).

Drug: Nivolumab; Drug: Relatlimab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation

Interventions

Nivolumab DRUG

240mg or 1 mg/kg administered IV

Also known as: Opdivo

Arm A; Arm B

Relatlimab DRUG

80mg administered IV

Also known as: BMS-986016, Anti-LAG3

Arm B

Carboplatin DRUG

standard care dose

Also known as: Paraplat, Paraplatin, Blastocarb, Carboplat, Carbosin, Carbosol, Carbotec, Displata, Ercar, Nealorin, Novoplatinum, Paraplatin AQ, Paraplatine, Platinwas

Arm A; Arm B

Paclitaxel DRUG

standard care dose

Also known as: Taxol, Anzatax, Asotax, Bristaxol, Praxel, Taxol Konzentrat

Arm A; Arm B

Radiation RADIATION

standard care dose

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Men and women aged ≥ 18 years old
• Histologically proven (squamous cell or adenocarcinoma) esophageal or gastro- esophageal junction cancer (core biopsy required).
• Stage II/III disease as per AJCC staging 7.0
• Baseline imaging with FDG-PET scan and endoscopic ultrasound within 28 days prior to registration
• ECOG performance status 0-1 (see Appendix B).
• Adequate oral intake/nutritional status without the need for enteral or parenteral feeding during chemoradiation or preoperative period
• Adequate organ function as follows:
• Leukocytes ≥ 2,000/mm3
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 2.0 mg/dL
• Bilirubin (total) within normal institutional limits (except subjects with Gilbert Syndrome who must have total bilirubin \< 3.0 mg/dL)
• AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 2.5 times the upper limit of normal
• PT such that international normalized ratio (INR) is ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin and a PTT ≤ upper limit of normal

You may not qualify if:

• Patient has active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Esophageal tumors that are located in the mid esophagus or higher i.e. not involving distal esophagus or GE junction.
• Tumors whose proximal end are higher that the level of the carina
• Biopsy proven involvement of supraclavicular lymph nodes
• Tumors must not extend 5cm or more into the stomach
• Patient has a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose. Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
• Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia) are excluded unless a complete remission was achieved at least 1 years prior to study entry and no additional therapy (other than adjuvant hormonal therapy for breast cancer) is required or anticipated to be required during the study period.
• Subjects with brain metastasis are excluded from this study and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
• Subjects with a history of interstitial lung disease.
• Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
• Known positive history or positive test for Human Immunodeficiency Virus or Acquired ImmunoDeficiency Syndrome (AIDS).
• History of allergy to study drug components.
• Women who are pregnant or nursing.
• WOBP and Men with female partners (WOCBP) that are not willing to use contraception.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Alleghany Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

Baylor University/ Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

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MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Interventions

Nivolumab; relatlimab; Carboplatin; Paclitaxel; Taxes; Radiation

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Physical Phenomena

Study Officials

• Vincent Lam, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: February 7, 2017
• Study Start: July 11, 2017
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)