Cancer type | Phase | Primary outcome | Dosing regimen | Enrollment number | Status | Results | Clinical trials identification number |
---|---|---|---|---|---|---|---|
Stage IV NSCLC | Phase 1 | Evaluation of treatment related toxicity of specified treatment regimen in ALK/EGFR mutated NSCLC patients for up to 36 months; secondary outcomes: OS, PFS, RR evaluated up to 36 months | Arm 1 (EGFR mutant NSCLC): 4 doses of IPI 3 mg/kg + erlotinib 150 mg OD (or the tolerable dose); arm 2 (ALK positive NSCLC): 4 doses of IPI 3 mg/kg + crizotinib 250 mg BID (or tolerable dose); arm 3 (EGFR mutant NSCLC): erlotinib 150 mg OD (or tolerable dose) + NIVO 240 mg Q2W; arm D (ALK positive NSCLC): crizotinib 250 mg BID (or tolerable dose) + NIVO 240 mg Q2W | 14 | Active, not recruiting | NA | NCT01998126 |
Stage IIIb/IV NSCLC | Phase 1 RCT | Evaluate safety of specified treatment regimens; secondary outcomes: Evaluation of ORR and PFS rate (time frame: up to 24 weeks) | Arm A: gemcitabine + cisplatin and NIVO; arm B: pemetrexed + cisplatin and NIVO; arm C: carboplatin + paclitaxel and NIVO; arm D: NIVO + maintenance with bevacizumab; arm E: erlotinib + NIVO; arm F: NIVO; arm G (squamous NSCLC): IPI + NIVO; arm H (non-squamous NSCLC): IPI + NIVO; arm I (squamous NSCLC): IPI + NIVO; arm J (non-squamous NSCLC): IPI + NIVO; arm K (squamous NSCLC): NIVO; arm L (non-squamous NSCLC): NIVO; arm M (NSCLC with asymptomatic and untreated brain metastases): NIVO; arm N (NSCLC with any histology): IPI + NIVO; arm O: IPI + NIVO; arm P: IPI + NIVO; arm Q: IPI + NIVO; arm R: IPI + NIVO; arm S: IPI + NIVO | 412 | Completed | NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q12W (n = 38): grade 3–4 TRAE: 37%, ORR: 47% (95%CI: 31–64), median PFS: 8.1 months (95%CI: 5.6–13.6), 1 year OS rate: not calculated; NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W (n = 39): grade 3–4 TRAE: 33%, ORR: 39% (95%CI: 23–55), median PFS: 3.9 months (95%CI: 2.6–13.2), 1 year OS rate: 69% (95% CI: 52–81); NIVO 3 mg/kg Q2W (n = 52): grade 3–4 TRAE: 19%, ORR: 23% (95%CI: 13–37), median PFS: 3.6 months (95%CI: 2.3–6.6), 1 year OS rate: 73% (95% CI: 59–83); ORR for tumors having PD-L1 expression of ≥1% was reported as 57% and ORR for tumors having PD-L1 expression of ≥50% was reported as 92% with NIVO + IPI; ORR for tumors having PD-L1 expression of ≥1% was reported as 28% and ORR for tumors having PD-L1 expression of ≥50% was reported as 50% with NIVO monotherapy | NCT01454102; CheckMate 012 [60] |
Advanced NSCLC | Phase 1b | OR assessed at 24 weeks, number of study participants experiencing DLT and number of participants that report treatment associated toxicities | Participants enrolled in dose escalation arm and all experimental arms receive MEDI4736 + tremelimumab combination therapy | 747 | Active, not recruiting, preliminary results available | OR in tremelimumab 1 mg/kg combination therapy cohort: Overall: 23% (6 of 26 patients, 95%CI: 9 to 44); PD-L1 positive tumors: 22% (2 of 9 patients, 95%CI: 3 to 60); PD-L1 negative tumors: 29% (4 of 14 patients, 95%CI: 8 to 58); MTD exceeded for therapy with tremelimumab 3 mg/kg + MEDI4736 20 mg/kg with DLT of 30% (2 of 6 patients) | NCT02000947 [62] |
NSCLC with brain metastases | Phase 1/Phase 2 | Recommended phase 2 dose of NIVO + stereotactic radiosurgery/ NIVO + whole brain radiation therapy/ NIVO + IPI and stereotactic radiosurgery/ NIVO + IPI and whole brain radiation therapy; the observed MTD from phase 1 to become the starting dose for phase 2 | Experimental arm 1: NIVO 3 mg/kg Q2W + stereotactic surgery; experimental arm 2: NIVO 3 mg/kg Q2W + whole brain radiation therapy 30 Gy in 10 fractions; experimental arm 3: NIVO MTD as decided in phase 1 + IPI 1 mg/kg Q6W and stereotactic radiosurgery; experimental arm 4: NIVO MTD as decided in phase 1 + IPI 1 mg/kg (Q6W) and whole brain radiation therapy (30 Gy in 10 fractions) | 80 | Not yet recruiting | NA | NCT02696993 |
Unresectable/metastatic NSCLC | Phase 1/ Phase 2 RCT | Part I: determine recommended phase 2 dose of PEMBRO; part II: OR rate for cohort G and H; secondary outcomes: PFS, OS and duration of response (assessed up to 2 years) | Cohort H: IPI + PEMBRO (recommended phase 2 dose as per cohort D) | 308 | Recruiting, preliminary data available | Not available for cohort H. | NCT02039674; KEYNOTE 021 [61] |
Advanced NSCLC | Phase 2 | Best ORR evaluated Q6W up to 48 weeks | IPI 1 mg/kg Q6W + NIVO 3 mg/kg Q2W | 35 | Recruiting | NA | NCT02350764 |
Stage IV NSCLC | Phase 2 | OR rate; secondary outcomes: PFS, duration of response (time frame: 6 months) | IPI + NIVO | 590 | Recruiting | NA | NCT02659059; CheckMate 568 |
Advanced NSCLC | Phase 2 RCT | PFS rate, ORR and duration of response (assessed up to 24 weeks) | Comparator arm: monotherapy with NIVO; arm 2: BMS-986016 + NIVO; arm 3: dasatinib + NIVO; arm 4: IPI + NIVO | 504 | Recruiting | NA | NCT02750514 |
Locally advanced/metastatic NSCLC | Phase 2 RCT | CR rate (assessed up to 2 years); secondary outcomes: ORR and disease control rate (assessed up to 2 years) | Arm 1: gefitinib + MEDI4736; arm 2: AZD9291 + MEDI4736; arm 3: docetaxel + selumetinib and MEDI4736; arm 4: tremelimumab + MEDI4736 | 49 | Completed | Not yet available | NCT02179671 |
Recurrent Stage IV squamous cell lung carcinoma | Phase 2/ Phase 3 RCT | ORR, OS (assessed for 3 years), IA-PFS (evaluated for 18 months), IA-PFS and OS in study participants receiving experimental regimen versus standard of care; secondary outcomes: duration of response, RR, PFS and OS for experimental regimen, frequency of toxicity events (assessed for 3 years) | S1400I arm I: IPI + NIVO; S1400I arm II: NIVO monotherapy | 10,000 | Recruiting | NA | NCT02154490; lung-MAP trial [79] |
Stage IV/recurrent NSCLC | Phase 3 | Percent study participants with high grade toxicity; secondary outcomes: PFS, ORR, duration of response (assessed for 40Â months) | NIVO + IPI | 1500 | Recruiting | NA | NCT02869789 |
NSCLC | Phase 3 RCT | Major pathological response rate (determined at surgery); secondary outcomes: complete pathological response rate (determined at surgery), OS and event free survival assessed for up to 130 months | Experimental arm: IPI + NIVO | 326 | Not yet recruiting | NA | NCT02998528 |
Stage IV squamous cell carcinoma | Phase 3 RCT | OS (time frame: 3Â years), IA-PFS (time frame: 18Â months) | Active comparator: NIVO on D1, repeated every 14Â days; experimental arm: NIVO + IPI D1 of every 3rd course, course to be repeated every 14Â days | 350 | Recruiting | NA | NCT02785952 |
Chemotherapy naïve/recurrent stage IV NSCLC | Phase 3 RCT | OS, assessed up to 48 months; PFS, assessed up to 40 months; Secondary outcome: OR rate, assessed up to 48 months | Arm A: NIVO monotherapy; arm B: IPI + NIVO combination therapy; arm C: platinum doublet chemo (carboplatin/ cisplatin + gemcitabine for squamous histology and carboplatin/ cisplatin + pemetrexed for non-squamous histology) + NIVO | 2220 | Recruiting | NA | NCT02477826; CheckMate 227 |
Stage IV/recurrent NSCLC | Phase 3 RCT | PFS for T790 M negative, EGFR positive NSCLC, evaluated for 33 months; secondary outcomes: PFS rate, ORR and duration of response evaluated for 33 months; OS assessed for 5 years | Arm 1: IPI + NIVO; arm 2: platinum doublet therapy (cisplatin/ carboplatin + pemetrexed) + NIVO | 465 | Recruiting | NA | NCT02864251; CheckMate 722 |
Advanced/metastatic NSCLC | Phase 3 RCT | OS with MEDI4736 + tremelimumab combination versus standard of care treatment (evaluated for 4 years) | Arm 1: MEDI4736 + tremelimumab | 800 | Recruiting | NA | NCT02542293; NEPTUNE study |
Locally advanced/metastatic NSCLC | Phase 3 RCT | PFS and OS assessed up to 3 years; secondary outcomes: ORR (evaluated for 3 years), proportion of study participants alive at end of 1 year of randomization and duration of response (evaluated for 3 years) | Sub-study-A experimental arm: participants with PD-L1 positive malignancy to receive MEDI4736; sub-study B experimental arm 1: participants with PD-L1 negative malignancy to receive MEDI4736 + tremelimumab; sub-study experimental arm 2: participants with PD-L1 negative malignancy to receive MEDI4736 only; sub-study B experimental arm 3: participants with PD-L1 negative malignancy to receive tremelimumab only | 730 | Active, not recruiting | NA | NCT02352948; ARCTIC study |
Advanced/metastatic NSCLC | Phase 3 RCT | OS and PFS with MEDI4736 + tremelimumab combination versus standard of care treatment (evaluated for up to 3 years) | Arm 1: MEDI4736 monotherapy; arm 2: MEDI4736 + tremelimumab | 1092 | Active, not recruiting | NA | NCT02453282; MYSTIC study |