Nivolumab in Combination With Chemotherapy, or Nivolumab in Combination With Ipilimumab, in Advanced EGFR-Mutant or ALK-Rearranged NSCLC

NCT03256136 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-011
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying a drug intervention as a possible treatment for lung cancer. The drugs involved in this study are:

• Nivolumab
• Carboplatin
• Pemetrexed
• Ipilimumab

Conditions

Lung Cancer

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR), Presented in Numbers of Participants

  Complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to approximately 2 years

Secondary Outcomes (4)

• Disease Control Rate (DCR), Presented in Numbers of Participants

  Up to approximately 2 years

• Progression Free Survival (PFS)

  From the start of treatment until disease progression or death due to any cause, up to approximately 2 years

• Overall Survival (OS)

  From the start of treatment until death due to any cause, up to approximately 2 years

• Duration Of Response

  From the first documented response until disease progression or death, up to approximately 2 years

Study Arms (4)

Nivolumab Plus Ipilimumab EGFR

EXPERIMENTAL

Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks

Drug: Nivolumab; Drug: Ipilimumab

Nivolumab Plus Ipilimumab ALK

EXPERIMENTAL

Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks

Drug: Nivolumab; Drug: Ipilimumab

Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive

EXPERIMENTAL

Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks

Drug: Carboplatin; Drug: Nivolumab; Drug: pemetrexed

Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive

EXPERIMENTAL

Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks

Drug: Carboplatin; Drug: Nivolumab; Drug: pemetrexed

Interventions

Carboplatin DRUG

Chemotherapy

Also known as: Paraplatin

Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive; Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive

Nivolumab DRUG

will allow the body's immune system to work against tumor cells

Also known as: Opdivo

Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive; Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive; Nivolumab Plus Ipilimumab ALK; Nivolumab Plus Ipilimumab EGFR

pemetrexed DRUG

Chemo therapy

Also known as: Alimta

Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive; Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive

Ipilimumab DRUG

will allow the body's immune system to work against tumor cells

Also known as: Yervoy

Nivolumab Plus Ipilimumab ALK; Nivolumab Plus Ipilimumab EGFR

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed advanced (stage IIIB or IV) non-small-cell lung cancer (NSCLC).
• ALK-rearranged NSCLC: ALK rearrangement as assessed by ALK FISH, IHC, or next-generation sequencing (NGS). For ALK FISH, rearrangements must be detected in \>15% of tumor cells.
• EGFR-mutant NSCLC: EGFR activating gene mutation (e.g., L858R, exon 19 deletion) as well as a T790M mutation per local testing.
• Presence of at least one measurable lesion as defined by RECIST v1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the completion of irradiation.
• Prior treatment with appropriate tyrosine kinase inhibitors (TKIs) as follows:
• ALK-positive NSCLC (cohorts B and D): Participants must have progressed on or after 1 or more next-generation ALK-TKI(s).
• EGFR-mutant NSCLC (cohorts A and C): Participants must have progressed on or after 1 or more third-generation, T790M mutant-selective EGFR-TKI(s).
• Prior systemic chemotherapy requirements are as follows:
• Nivolumab plus carboplatin and pemetrexed arms (cohorts A and B): NO prior systemic chemotherapy is allowed. NOTE: Prior adjuvant or neoadjuvant chemotherapy is allowed if received more than 12 months prior to the study.
• Nivolumab plus ipilimumab arms (cohorts C and D): Participants must have received a platinum-based combination chemotherapy for their advanced lung cancer and either progressed on/after this chemotherapy or are intolerant. Only ONE line of chemotherapy is allowed. NOTE: Prior adjuvant or neoadjuvant chemotherapy does not count as an additional line of chemotherapy if received more than 12 months prior to the study.
• Tumor tissue sample is required following the participant's last line of systemic therapy (TKI or chemotherapy). Tissue sample may be fresh (core needle, excisional, or incisional biopsy), or archival if obtained within 6 months prior to enrollment. There can have been no systemic therapy administered after the sample was obtained. If a tissue sample is available but it has been \> 6 months and there has been no intervening therapy, the Principal Investigator may approve the sample after discussion. PD-L1 IHC testing will be performed on the tumor tissue, but positivity on the PD-L1 IHC testing is not required to enroll in the study.
• Clinically asymptomatic and stable central nervous system (CNS) metastases are allowed (including untreated CNS metastases) if they have not required increasing doses of steroids or stable doses equivalent to prednisone \> 10 mg daily within 2 weeks prior to study entry for CNS symptoms.
• Prior palliative radiotherapy must have been completed at least 2 weeks prior to study entry.
• Subjects must have been off any prior systemic anti-cancer treatment (including TKIs) for at least 5 half-lives of that drug.
• Age ≥ 18 years old.

You may not qualify if:

• Subjects previously treated with T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents.
• Subjects with symptomatic brain metastases, carcinomatous meningitis, spinal cord compression, or intractable back pain due to compression of destructive mass.
• Subjects with active, known, or suspected autoimmune disease. Subjects 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.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization (unless used to treat investigational drug-related adverse events). Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Subjects with interstitial lung disease or interstitial pneumonitis that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days prior to screening. No major surgery, other than diagnostic surgery, is allowed within 4 weeks prior to treatment in the study.
• Co-administration of anti-cancer therapies other than those administered in the study.
• Subjects with other active malignancy requiring concurrent intervention.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). HIV-positive participants are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because there is the potential for pharmacokinetic interactions with combination antiretroviral therapy and study drugs.
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
• Subjects with ≥ grade 2 peripheral neuropathy at enrollment per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
• Pregnant or lactating women. Pregnant women are excluded from this study because the study drugs (i.e., nivolumab, ipilimumab, carboplatin, and pemetrexed) have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued.
• Subjects currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug.
• History of allergy or hypersensitivity to any study drugs or their excipients.
• Any known clinically significant concomitant medical condition, laboratory abnormality, or psychiatric illness that, in the investigator's opinion, would prevent the subject from participating in the study, pose an unacceptable risk to the patient in this study, or interfere with the interpretation of safety results.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts general Hospital

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; Nivolumab; Pemetrexed; Ipilimumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Jessica Lin
• Organization: Massachusetts General Hospital

jjlin1@partners.org

617-724-1134

Study Officials

• Alice Shaw, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Thoracic Cancers

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 21, 2017
• Study Start: November 22, 2017
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: November 4, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)