Radiation and Immune Checkpoints Blockade in Metastatic NSCLC (BMS # CA209-632)

NCT03168464 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: 1607017434
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

NSCLC patients with metastatic disease who have failed at least one prior treatment and have a minimum of two metastatic lesions (at least one measurable), are eligible if they have an ECOG Performance Status of 0-1. Patients will receive on Day 1, ipilimumab (every 6 weeks) concurrently with radiation (6Gy x 5 fractions). Nivolumab (every 2 weeks) will be given in addition to ipilimumab on day 22.

Conditions

Non Small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Enhance Overall Response Rate (ORR) to the Combination of Ipi/Nivo in Chemo-refractory NSCLC and Double the ORR of Ipi/RT, From 18% Based on Intent to Treat to 36%.

  To enhance the ORR to the combination of Ipi/Nivo in chemo-refractory NSCLC by preceding it with a combination of Ipi/RT to convert the irradiated tumor into an in situ vaccine and to double the ORR of Ipi/RT, from 18% based on intent to treat to 36%.

  2.5 Months, 6 Months, 3 years

Secondary Outcomes (7)

• Changes in T-cell Receptor (TCR) Repertoire in Peripheral Blood Are Associated With Response to Treatment

  4 years

• Serum Markers IFN-b, CXCL11, sMICA, sMICB Levels/Changes Associated With Patients' Response to the Treatment.

  4 years

• Associations of Overall Response Rate (ORR) With Changes in the Microbiome

  4 years

• Progression Free Survival

  4 years

• Patients' Time to Progression Will be Assessed in This Study.

  3 years

Study Arms (1)

Immunotherapy + Radiation

EXPERIMENTAL

Non-ablative radiotherapy (6GyX5) is directed to one lesion during a first immunotherapy treatment with Ipilimumab 3 mg/kg (± 24hrs from first RT dose). On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.

Drug: Ipilimumab; Drug: Nivolumab; Radiation: Radiation therapy

Interventions

Ipilimumab DRUG

Ipilimumab (3mg/kg) is given concurrently (+/- 24hrs from first RT dose) with radiation therapy on Day 1 of the study. On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.

Also known as: Yervoy

Immunotherapy + Radiation

Nivolumab DRUG

On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.

Also known as: OPDIVO

Immunotherapy + Radiation

Radiation therapy RADIATION

Ipilimumab (3mg/kg) is given concurrently (+/- 24hrs from first RT dose) with radiation therapy on Day 1 of the study.

Immunotherapy + Radiation

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document;
• Histologic diagnosis of NSCLC;
• Any Kras or epidermal growth factor receptor (EGFR) status is permitted; Patients with an EGFR sensitizing mutation must have received an EGFR tyrosine kinase inhibitor (either erlotinib, gefitinib or afatinib) and patients with anaplastic lymphoma kinase (ALK) translocation must have received anti-ALK therapy.
• Patients must have at least two distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter. Patients may have additional non-measurable metastatic lesions (e.g., bone metastases);
• Patients must have prior treatment with at least one line of therapy for metastatic NSCLC. Any prior therapy is permitted except prior therapy with ipilimumab, other anti cytotoxic T-lymphocyte-associated protein (CTLA) agents or Checkpoint inhibitors;
• An interval of 2 weeks from last previous therapy is required;
• Patients must have recovered from the toxic effect(s) of the most recent anti-cancer treatment to NCI CTCAE Grade 1 or less (except alopecia).
• Patients must have adequate organ and marrow function as defined by initial laboratory tests:
• white blood cell (WBC) ≥ 2000/uL
• absolute neutrophil count (ANC) ≥ 1.5/uL
• Platelets ≥ 100 x 103/uL
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
• Bilirubin ≤ 1.5 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin ≤ 3.0 mg/dL;

You may not qualify if:

• Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
• Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic auto immune disease (e.g., rheumatoid arthritis, progressive systemic sclerosis \[scleroderma\]), systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\];
• Patients with a history of symptomatic interstitial lung disease OR a history of (non-infectious) pneumonitis that required oral or IV steroids or current pneumonitis.
• Patients with active HIV infection Patients with Hepatitis B and Hepatitis C infection.
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea;
• Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; Tyrosine Kinase inhibitors such as erlotinib;
• Prior therapy with ipilimumab or another anti-CTLA-4 antagonist;
• Women and men who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 5mos (women) or 7mos(men) weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

Ipilimumab; Nivolumab; Radiotherapy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Limitations and Caveats

The study was terminated early leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Sharanya Chandrasekhar
• Organization: Weill Cornell Medicine

shc2043@med.cornell.edu

646-962-3110

Study Officials

• Silvia Formenti, M.D.

  Weill Cornell Medicine New York Prebyterian hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Eligible patients will receive on Day 1 ipilimumab 3mg/kg concurrently with Radiation therapy (6GY x 5 fractions). On Day 22, patients will receive nivolumab 240mg (every 2 weeks) in addition to ipilimumab (1mg/kg). Patients will be evaluated for response at Day 70 (+/- 7 days) for progression.

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: May 30, 2017
• Study Start: October 9, 2017
• Primary Completion: March 11, 2022
• Study Completion: March 11, 2022
• Last Updated: April 24, 2023
• Results First Posted: April 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)