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Gastroesophageal CancerPhase 1/2REACTIONNCT03610711

REACTION (Radiation Enhanced Assessment of Combination Therapies in Immuno-ONcology) - Nivolumab or Nivolumab in Combination With Other Immuno-oncology (IO) Agents After Targeted Systemic Radiation in Patients With Advanced Esophagogastric Cancer

A Phase 1/2 study testing Nivolumab and Relatlimab in people with Gastroesophageal Cancer and Immune Checkpoint Inhibition, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a Phase 1B study assessing the safety of immune checkpoint inhibition after SBRT in patients with recurrent or metastatic gastroesophageal cancer (limited metastatic disease). Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Nivolumab and Relatlimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
3 sitesUnited States
Study dates
6 Mar 2019to Dec 2027
Phase
Phase 1/2
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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women aged ≥ 18 years old.
  • Histologically proven (squamous cell or adenocarcinoma) esophageal or gastro-esophageal junction cancer or gastric cancer (core biopsy required)
  • Either a formalin fixed paraffin block or a minimum of ten 5-micron tissue section's (slides) of tumor biopsy sample must be available for biomarker evaluation.
  • Recurrent disease or Stage IV disease as per American Joint Committee on Cancer (AJCC) staging 8.0 - patients who decline systemic chemotherapy in the first line metastatic setting are eligible.
  • (Relatlimab arm only) LVEF assessment with documented left ventricular ejection fraction ( LVEF) >/=50% by either echocardiogram TTE or multigated acquisition scan (MUGA) (TTE preferred test) within 6 months from first study drug administration,whichever is most recent.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
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  • 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)
  • Aspartate aminotransferase (AST) (SGOT), Alanine Aminotransferase (ALT) (SGPT), and alkaline phosphatase ≤ 2.5 times the institutional upper limit of normal
  • prothrombin time (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 partial thromboplastin time (PTT) ≤ institutional upper limit of normal
  • Adequate cardiac function as defined by: no evidence of (PR) prolongation or Atrioventricular block (AV block) on baseline electrocardiogram (ECG).
  • The effects of nivolumab, relatlimab or BMS-986178, on the developing human fetus are unknown. For this reason women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 5 months after the last dose of nivolumab +/- IO therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for 7 months after the last dose of nivolumab +/- IO therapy. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration.
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (see Appendix 4) for the duration of treatment with study treatment(s) plus 33 weeks after the last dose of the study treatment (ie, 90 days [duration of sperm turnover] plus the time required for nivolumab and relatlimab to undergo approximately 5 half-lives). In addition, male participants must be willing to refrain from sperm donation during this time.
  • Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated Institutional Review Board (IRB) approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report Adverse Events (AEs), understand the drug dosing schedule and use of medications to control AEs.

Who cannot join

  • Any active or history of autoimmune disease (including any history of inflammatory bowel disease), or history of syndrome that required systemic steroids or immune-suppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy.
  • (Relatlimab arm only) Troponin T (TnT) or I (TnI) > 2 × institutional upper limit of normal (ULN). Subjects with TnT or TnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤1 x ULN. If TnT or TnI levels are > 1 to 2 × ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the BMS Medical Monitor or designee. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 x ULN, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the Bristol Myers Squibb (BMS) Medical Monitor or designee.
  • (Relatlimab arm only) Participants must not have a history of myocarditis
  • (Relatlimab arm only) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
  • Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
  • Uncontrolled angina within the 3 months prior to consent
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  • Any history of clinically significant arrhythmias (such as ventricular tachycardia, poorly controlled atrial fibrillation, ventricular fibrillation, or torsades de pointes)
  • Corrected QT interval (QTc) prolongation > 480 msec
  • History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association (NYHA) functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, , poorly controlled venous thrombosis etc.)
  • Cardiovascular disease-related requirement for daily supplemental oxygen
  • History of two or more MIs OR two or more coronary revascularization procedures
  • (Relatlimab arm only) LVEF (Left Ventricular Ejection Fraction) assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred test) within 6 months from first study drug administration.
  • Ongoing requirement for systemic corticosteroids. However, inhalational steroids are allowed.
  • 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 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
  • Subjects with known brain metastasis are excluded from this study. Patients with suspected brain metastasis must have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
  • Subjects with a history of interstitial lung disease. Patients requiring continuous supplemental oxygen are excluded.
  • Use of any vaccines against infectious diseases (e.g., influenza, varicella. etc.) within 4 weeks (28 days) of initiation of study therapy.
  • 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.
  • Men with female partners (WOCBP) that are not willing to use contraception
  • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug or radiation hazardous or obscure the interpretation of toxicity or adverse events.
  • Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Baylor University

    Dallas, Texas, 75246

  • Alleghany Health Network

    Pittsburgh, Pennsylvania, 15212

Other trials in United States

About this study

This is a Phase 1B study assessing the safety of immune checkpoint inhibition after SBRT in patients with recurrent or metastatic gastroesophageal cancer (limited metastatic disease).

Read the detailed description

This is a Phase 1B study assessing the safety of immune checkpoint inhibition after SBRT in patients with recurrent or metastatic gastroesophageal cancer (limited metastatic disease). Arm A explores the safety and efficacy of nivolumab alone, and Arm B explores the safety and efficacy of nivolumab plus Relatlimib. Patients with recurrent or metastatic esophagogastric cancer are eligible for this study which will enroll patients with limited disease burden and who are Programmed death-1(PD-1) therapy naïve. This will allow for us to assess if systemic ablative radiation (SBRT to multiple metastatic sites plus PD-1/ anti-LAG3) is able to enhance the effectiveness of nivolumab +/- anti-LAG3 or to overcome treatment resistance mechanisms. Patients will be treated with targeted high dose radiation (SBRT) to metastatic lesions as outlined below. One of the lesions which is considered the easiest to biopsy and not causing symptoms will not be radiated so as to obtain tissue for correlative analysis. This lesion will then be re-biopsied approx. 4 weeks after the completion of radiation to the other metastatic sites. If a lesion is causing pain or other symptoms this site will not be chosen as the biopsiable site. The chosen metastatic lesion can then be irradiated at a later date if we do not see disease response in that region. Approximately 21 patients will be enrolled on study with 6 enrolled on Arm A, and 15 enrolled on Arm B.

Being tested
Nivolumab, Relatlimab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Optivo

    240mg administered IV over 30 minutes every 2 weeks for one year

  • RelatlimabDrug

    Also called anti-LAG3

    every 2 weeks for one year

Study groups in NCT03610711
Study groupRoleWhat they receive
Arm A Nivolumab OnlyExperimentalstereotactic body radiation (SBRT) 8G x 3 followed by Nivolumab 240mg administered IV over 30 minutes every 2 weeks for one year or until evidence of disease progression or unresolved toxicity.
Receives: Drug: Nivolumab
Arm B Nivolumab + RelatlimabExperimentalstereotactic body radiation (SBRT) 8G x 3 followed by Nivolumab 240mg administered IV over 30 minutes every 2 weeks and Relatlimab (anti-LAG3) every 2 weeks for one year or until evidence of disease progression or unresolved toxicity.
Receives: Drug: Nivolumab; Drug: Relatlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in the infiltrating CD8+ T cell density units after systemic treatment with radiation plus nivolumab +/- Relatlimib

    Change in the infiltrating CD8+ T cell density units pre- and post-systemic treatment with radiation plus nivolumab +/- Relatlimib in the non-irradiated metastatic lesion.

    Measured: 5 years

Secondary outcomes (2)

  1. Safety profile of nivolumab +/- Relatlimib plus systemic radiation as determined by number of drug-related adverse events

    Number of drug-related adverse events Grade 3 or higher as defined by CTCAE 5.0 (CTCAE v5.0).

    Measured: 5 years

  2. Efficacy of PD-1 inhibition +/- Relatlimib as determined by number of participants without evidence of disease progression

    Measured: 3 months post targeted radiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2018
  2. Study start6 Mar 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
Single blind
Who is masked
Participant
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03610711
Sponsor's protocol ID
J1884
Other IDs
IRB00166032, CA224-053
Acronym
REACTION
Status last verified
May 2026
First submitted
26 Jul 2018
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. doi: 10.1016/S0140-6736(17)31827-5. Epub 2017 Oct 6.

    PubMed 28993052

  • Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.

    PubMed 26028255

  • Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014 Sep 11;513(7517):202-9. doi: 10.1038/nature13480. Epub 2014 Jul 23.

    PubMed 25079317

  • Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013 Aug 28;5(200):200ra116. doi: 10.1126/scitranslmed.3006504.

    PubMed 23986400

  • Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, Yang S, Duncan M, Ahuja N, Taube JM, Anders RA, Kelly RJ. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017 May;66(5):794-801. doi: 10.1136/gutjnl-2015-310839. Epub 2016 Jan 22.

    PubMed 26801886

  • Derks S, Nason KS, Liao X, Stachler MD, Liu KX, Liu JB, Sicinska E, Goldberg MS, Freeman GJ, Rodig SJ, Davison JM, Bass AJ. Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma. Cancer Immunol Res. 2015 Oct;3(10):1123-1129. doi: 10.1158/2326-6066.CIR-15-0046. Epub 2015 Jun 16.

    PubMed 26081225

  • Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin CC, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M, Bang YJ. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016 Jun;17(6):717-726. doi: 10.1016/S1470-2045(16)00175-3. Epub 2016 May 3.

    PubMed 27157491

  • Derks S, Liao X, Chiaravalli AM, Xu X, Camargo MC, Solcia E, Sessa F, Fleitas T, Freeman GJ, Rodig SJ, Rabkin CS, Bass AJ. Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016 May 31;7(22):32925-32. doi: 10.18632/oncotarget.9076.

    PubMed 27147580

  • McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, Watkins TB, Shafi S, Murugaesu N, Mitter R, Akarca AU, Linares J, Marafioti T, Henry JY, Van Allen EM, Miao D, Schilling B, Schadendorf D, Garraway LA, Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD, Shukla SA, Wu CJ, Peggs KS, Chan TA, Hadrup SR, Quezada SA, Swanton C. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016 Mar 25;351(6280):1463-9. doi: 10.1126/science.aaf1490. Epub 2016 Mar 3.

    PubMed 26940869

  • Attwood SE, Smyrk TC, DeMeester TR, Mirvish SS, Stein HJ, Hinder RA. Duodenoesophageal reflux and the development of esophageal adenocarcinoma in rats. Surgery. 1992 May;111(5):503-10.

    PubMed 1598670

  • Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, Zhang M, Papadopoulos N, Kinzler KW, Vogelstein B, Sears CL, Anders RA, Pardoll DM, Housseau F. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015 Jan;5(1):43-51. doi: 10.1158/2159-8290.CD-14-0863. Epub 2014 Oct 30.

    PubMed 25358689

  • Pera M, Brito MJ, Poulsom R, Riera E, Grande L, Hanby A, Wright NA. Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats. Carcinogenesis. 2000 Aug;21(8):1587-91.

    PubMed 10910963

  • Zaidi AH, Saldin LT, Kelly LA, Bergal L, Londono R, Kosovec JE, Komatsu Y, Kasi PM, Shetty AA, Keane TJ, Thakkar SJ, Huleihel L, Landreneau RJ, Badylak SF, Jobe BA. MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model. PLoS One. 2015 Mar 31;10(3):e0122375. doi: 10.1371/journal.pone.0122375. eCollection 2015.

    PubMed 25826212

  • Bonde P, Sui G, Dhara S, Wang J, Broor A, Kim IF, Wiley JE, Marti G, Duncan M, Jaffee E, Montgomery E, Maitra A, Harmon JW. Cytogenetic characterization and gene expression profiling in the rat reflux-induced esophageal tumor model. J Thorac Cardiovasc Surg. 2007 Mar;133(3):763-9. doi: 10.1016/j.jtcvs.2006.07.044.

    PubMed 17320581

  • Gibson MK, Zaidi AH, Davison JM, Sanz AF, Hough B, Komatsu Y, Kosovec JE, Bhatt A, Malhotra U, Foxwell T, Rotoloni CL, Hoppo T, Jobe BA. Prevention of Barrett esophagus and esophageal adenocarcinoma by smoothened inhibitor in a rat model of gastroesophageal reflux disease. Ann Surg. 2013 Jul;258(1):82-8. doi: 10.1097/SLA.0b013e318270500d.

    PubMed 23108119

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and Relatlimab in people with Gastroesophageal Cancer and Immune Checkpoint Inhibition, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites 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 19 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the infiltrating CD8+ T cell density units after systemic treatment with radiation plus nivolumab +/- Relatlimib (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03610711, which also lists 33 linked publications.

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 6 May 2026.

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