Phase 1
Completed 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)
Source: ClinicalTrials.gov NCT01454102 ↗Enrolled (actual)
376
Serious AEs
52.4%
Results posted
Aug 2019
Primary outcomePrimary: Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death — 4; 10; 8; 3 Participants
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.
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 | — |
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. Informational only — not medical advice.