Table 1.

Ongoing trials with anti-PD-1/PD-L1 plus anti-CTLA-4 agents in advanced and metastatic NSCLC.

NCT number	Study population	Treatment regimen	Phase	Important primary outcome	Status	Sponsor
Ongoing clinical trials with nivolumab and ipilimumab
NCT03377023	Treatment naïve or pretreated advanced or metastatic NSCLC	Nivolumab plus ipilimumab plus nintedanib	Phase I/II nonrandomized, parallel assignment	Phase I: MTD Phase II: ORR	Recruiting	H. Lee Moffitt Cancer Center
NCT02983045	NSCLC cohort consists of treatment naïve, IO naïve, and post anti-PD-1/PD-L1 relapsed or refractory patients	Two experimental arms NKTR-214 plus nivolumab and ipilimumab NKTR-214 plus nivolumab	Phase I/II, nonrandomized, parallel assignment	Safety, tolerability, ORR	Recruiting	Nektar Therapeutics
NCT03509584	Advanced NSCLC patients that have received at least one prior line of therapy and eligible for localized palliative XRT	Four experimental arms Part #1 NSCLC patients with bone metastasis eligible for localized hypofractionated radiotherapy will receive either nivolumab alone or nivolumab plus ipilimumab with hypofractionated XRT NSCLC patients eligible for localized radiotherapy of one target lesion (outside the brain) will receive either nivolumab alone or nivolumab plus ipilimumab with hypofractionated XRT	Phase I, randomized, parallel assignment	Incidence of immune-related adverse events	Not yet recruiting	Assistance Publique Hopitaux De Marseille
NCT03001882 (Checkmate 592)	Stage IV or recurrent NSCLC with no prior systemic therapy	Nivolumab plus ipilimumab	Phase II, single group assignment	ORR	Recruiting	Bristol-Myers-Squibb
NCT03425331	Stage IV NSCLC with no prior systemic anticancer therapy	Nivolumab plus ipilimumab	Phase II, single group assignment	Best overall ORR	Recruiting	Dana-Farber Cancer Center
NCT03573947 (TOP1705)	Stage IV NSCLC with no prior systemic anticancer therapy	Nivolumab, ipilimumab, and paclitaxel	Phase II, single group assignment	PFS	Recruiting	Jeffery Clarke, Duke University
NCT03215706 (Checkmate 9LA)	Stage IV NSCLC with no prior systemic anticancer therapy	Experimental arm: nivolumab plus ipilimumab with carboplatin/cisplatin and pemetrexed or paclitaxel Active comparator arm: carboplatin/cisplatin and pemetrexed or paclitaxel	Phase III, randomized, parallel assignment	OS	Recruiting	Bristol-Myers-Squibb
NCT03469960 (DICIPLE)	Stage IV NSCLC with no prior systemic anticancer therapy	Experimental arm: 6 months of induction treatment with nivolumab and ipilimumab followed by observation and nivolumab and ipilimumab in case of progression Active comparator arm: 6 months of induction treatment with nivolumab and ipilimumab followed by nivolumab and ipilimumab	Phase III, randomized, parallel assignment	PFS	Recruiting	Intergroupe Francophone de Cancerologie Thoracique
Ongoing trials with durvalumab and tremelimumab
NCT03275597	Chemotherapy naïve or pretreated patients with stage IV NSCLC with six or less extracranial sites for SBRT	Single experimental arm SBRT followed by durvalumab 1500 mg every 4 weeks plus tremelimumab 75 mg every 4 weeks for up to 4 doses.	Phase Ib, single group assignment	Safety and tolerability	Recruiting	University of Wisconsin
NCT03057106	Treatment naïve stage IV NSCLC	Two arms Durvalumab plus tremelimumab Four cycles of platinum plus gemcitabine or pemetrexed with durvalumab plus tremelimumab (every 3 weeks for four cycles) followed by maintenance durvalumab alone in squamous histology and pemetrexed plus durvalumab in nonsquamous histology.	Phase II, randomized, parallel assignment	OS	Active, not recruiting	Canadian Cancer Trials Group
NCT03164616 (POSEIDON)	Treatment naïve stage IV NSCLC	Two experimental arms and one comparator arm Experimental arm: durvalumab and tremelimumab plus standard of care (SoC) chemotherapy (CT) Experimental arm: durvalumab plus SoC CT Comparator arm: SoC CT alone	Phase III, randomized, parallel assignment	PFS and OS	Recruiting	AstraZeneca
Ongoing clinical trials with other anti-PD-1/PD-L1 and anti-CTLA-4 agents
NCT03527251	Locally advanced or metastatic NSCLC	Ipilimumab 1 mg/kg every 34 weeks for two doses followed by anti PD-1 antibody SHR-1210	Phase 1	Safety	Recruiting	Sun Yat-sen University
NCT03580694	Nonsquamous NSCLC with unresectable stage IIIB or stage IV	Two experimental arms Single dose. escalation cohort: cemiplimab (anti-PD-1 mAb) Combination therapy, dose escalation, and dose expansion REGN4659 (anti-CTLA-1 mAb) and cemiplimab	Phase 1	DLTs, TRAEs, irAEs, SAEs, ORR, PK for cemiplimab and REGN4656	Recruiting	Regeneron pharmaceuticals
NCT03430063 (EMPOWER-Lung 4)	Stage IIIB/IIIC not candidates for concurrent chemoradiation and stage IV NSCLC	Three experimental arms Standard dose cemiplimab (REGN2810) High dose cemiplimab (REGN2810) Combination cemiplimab (REGN2810) and ipilimumab	Phase II, randomized, open label	ORR	Active, not recruiting	Regeneron pharmaceuticals and Sanofi
NCT03302234 (Keynote 589)	Treatment naïve stage IV NSCLC with PD-L1>/=50%	Two experimental arms Pembrolizumab 200 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks Pembrolizumab 200 mg every 3 weeks plus placebo	Phase III, randomized, double blinded	OS and PFS	Active, not recruiting	Merck Sharp and Dohme
NCT03515629 (EMPOWER-Lung 2)	Treatment naïve recurrent or metastatic NSCLC with tumor PD-L1 expression>/=50%	Two experimental arms with one active comparator Experimental arm Cemiplmab (REGN2810) plus ipilimumab Cemplimab (REGN280) plus chemotherapy plus ipilimumab Comparator arm Pembrolizumab	Phase III, randomized, open label, parallel assignment	PFS	Active, not recruiting	Regeneron pharmaceuticals

Obtained from clinicaltrials.gov, accessed: June 15, 2019.

DLT, dose-limiting toxicity; irAE, immune-related adverse events; MTD, maximum-tolerated dose; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; RR, response rate; SAEs, serious adverse events; TRAEs, treatment-related adverse events.