A Phase II Study of Nivolumab in Combination With Carboplatin and Pemetrexed, or Nivolumab in Combination With Ipilimumab, in Patients With Advanced, EGFR-mutant or ALK-rearranged, Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Lung Cancer
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 9
- Locations
- 3
- Primary Endpoint
- Objective Response Rate (ORR), Presented in Numbers of Participants
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. The FDA (the U.S. Food and Drug Administration) has approved Nivolumab as a treatment for other types of cancers including lung cancer. However, the combination of Nivolumab with other drugs (such as those being tested in this study) has not been approved by the FDA as a treatment for this type of lung cancer. The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of the drug Nivolumab in combination with standard of care chemotherapies, or in combination with Ipilimumab. Nivolumab and Ipilimumab are antibodies (a type of human protein) that are being tested to see if they will allow the body's immune system to work against tumor cells. This study is being done to see if Nivolumab and Ipilimumab, or Nivolumab and chemotherapy drugs (Carboplatin and Pemetrexed), are more effective against cancer when administered together. These drugs are given as infusions. They are designed to "boost" the immune system's ability to suppress or kill cancer cells that are foreign to the human body.
Investigators
Alice Shaw
Director, Center for Thoracic Cancers
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Nivolumab Plus Ipilimumab EGFR
Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks
Intervention: Nivolumab
Nivolumab Plus Ipilimumab EGFR
Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks
Intervention: Ipilimumab
Nivolumab Plus Ipilimumab ALK
Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks
Intervention: Nivolumab
Nivolumab Plus Ipilimumab ALK
Nivolumab administered intravenously every 2 weeks Ipilimumab administered intravenously every 6 weeks
Intervention: Ipilimumab
Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive
Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Intervention: Carboplatin
Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive
Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Intervention: Nivolumab
Nivolumab + Carboplatin + Pemetrexed with EGFR Chemo naive
Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Intervention: pemetrexed
Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive
Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Intervention: Carboplatin
Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive
Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Intervention: Nivolumab
Nivolumab + Carboplatin + Pemetrexed ALK Chemo naive
Nivolumab administered intravenously every 3 weeks Carboplatin administered intravenously every 3 weeks Pemetrexed administered intravenously every 3 weeks
Intervention: pemetrexed
Outcomes
Primary Outcomes
Objective Response Rate (ORR), Presented in Numbers of Participants
Time Frame: Up to approximately 2 years
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.
Secondary Outcomes
- 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)