Phase 1
N=376
Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012)
Non-small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01454102 ↗Enrolled (actual)
376
Serious AEs
52.4%
Results posted
Aug 2019
Primary outcome: Primary: Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death — 4; 10; 8; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Nivolumab (Biological); Gemcitabine (Drug); Cisplatin (Drug); Pemetrexed (Drug); Paclitaxel (Drug); Carboplatin (Drug); Bevacizumab (Drug); Erlotinib (Drug); Ipilimumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Jul 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death |
4; 10; 8; 3; 11; 23 | — |
| PRIMARY Number of Participants Who Experienced Selected Adverse Events |
3; 2; 0; 2; 4; 8 | — |
| PRIMARY Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests |
0; 0; 2; 1; 4; 2 | — |
| PRIMARY Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests |
2; 3; 1; 8; 12; 21 | — |
| SECONDARY Objective Response Rate (ORR) |
41.7; 46.7; 46.7; 16.7; 19.0; 23.1 | — |
| SECONDARY Progression-Free Survival Rate (PFSR) at Week 24 |
50.5; 68.4; 34.3; 58.3; 50.6; 39.7 | — |
Summary
* The study is evaluating the safety and tolerability of Nivolumab (BMS-936558) when combined with three platinum-based doublet chemotherapy regimens (Cisplatin/Gemcitabine; Cisplatin/Pemetrexed; and Carboplatin/Paclitaxel) in subjects with NSCLC.
* The study is evaluating the safety and tolerability of Nivolumab as maintenance therapy in combination with Bevacizumab/Avastin that will be given after at least 4 cycles of platinum doublet chemotherapy.
* The study is evaluating the safety and tolerability of Nivolumab in combination with Erlotinib among epidermal growth factor receptor (EGFR) mutation positive non-squamous NSCLC subjects and as monotherapy in subjects with NSCLC.
* The study is evaluating the safety and tolerability of Nivolumab in combination with Ipilimumab in subjects with squamous and non-squamous NSCLC.
* The study is evaluating the safety and tolerability of Nivolumab as switch maintenance therapy in subjects with squamous and non-squamous NSCLC.
* The study is evaluating the safety and tolerability of Nivolumab as monotherapy among subjects with untreated, asymptomatic brain metastases and no evidence of cerebral edema.
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria
- Newly diagnosed and confirmed Stage IIIB/IV NSCLC
- Previously treated NSCLC with asymptomatic brain metastases (eligible for Arm M) See additional details below
- Men and women aged ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Subject must be chemotherapy naive (except Arm D, K, L and M). Prior use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is acceptable. For Arms D, K, and L, subjects must be non-progressors within 42 days after completion of first-line treatment with ≥4 cycles of Platinum Doublet chemotherapy with or without Bevacizumab. See below for Arm M
- Either a formalin fixed tissue block or a minimum of 10 slides of tumor sample (archived or fresh) must be available for biomarker evaluation (a local pathologist must review for adequacy of sampling)
- Life expectancy of at least 3 months
- Prior radiotherapy must have been completed at least 2 weeks prior to study entry
For Arm M:
- No more than 4 brain metastases
- Each brain metastases ≤3 cm in size
- No evidence of cerebral edema
- Subjects must be free of neurologic symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroids for ≥10 days prior to initiation of study treatment
- At least 1 measurable target brain lesion >0.5 cm and no larger than 3 cm in diameter and/or 2 measurable brain target lesions >0.3 cm
- No prior radiation therapy, surgery, or other local therapy for target brain lesions
- Must have received at least one prior systemic anticancer therapy for NSCLC
Exclusion Criteria
- Subjects with symptomatic brain metastases, spinal cord compression, or intractable back pain due to a compressive or destructive mass
- Subjects who require emergent use of systemic steroids, emergent surgery and/or radiotherapy
- Any active or history of a known autoimmune disease
- Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, gastric, or colon cancers or cervical cancers/dysplasia, or breast carcinoma in situ) 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
- History of Grade ≥2 neuropathy
- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
Data sourced from ClinicalTrials.gov (NCT01454102). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.