Table 3 Phase 1 solid tumor trials investigating combined immunotherapy with anti-CTLA-4 plus anti- PD-1/PD-L1 monoclonal antibodies
Cancer type | Phase | Primary outcome | Dosing regimen | Enrollment number | Status | Results | Reference/ Clinical trials identification number |
|---|---|---|---|---|---|---|---|
HIV associated unresectable metastatic solid tumors | Phase 1 | MTD of NIVO (time frame: 56 days) | NIVO on D1; study participants in dose level 2 receive IPI on 1st day of every 3rd course of NIVO while those in dose level − 2 receive IPI on 1st day of every 6th course of NIVO; treatment repeated every 14 days for 46 cycles of NIVO | 42 | Recruiting | NA | NCT02408861 |
Locally advanced/metastatic solid tumors | Phase 1 | Incidence of TRAE (evaluated up to 30 days after completion of therapy) and the incidence of DLT (assessed for 21 days from initiation of treatment); secondary outcomes: OS, PFS, duration of response, OR and best overall response assessed for 3 years | Arm A: atezolizumab + IPI Q3W for 4 cycles; arm B: Interferon alfa-2b (3 doses/week) + atezolizumab Q3W | 200 | Recruiting | NA | NCT02174172 |
Advanced incurable solid malignancies | Phase 1b | Determine RP2D tremelimumab with/ without MEDI4736 in patients on treatment with standard of care chemotherapy (assessed up to 2Â years) | Tremelimumab (D1 of cycles 1, 3 and 5, or, D1 of cycle 1) with/without MEDI4736 (Q3W) | 150 | Recruiting | NA | NCT02537418 |
Advanced solid tumors/relapsed metastatic SCCHN | Phase 1/ Phase 2 | Determine the MTD and RP2D; assessment of safety and efficacy of specified treatment regimen; evaluation of ORR for up to 12 months | Experimental part A1: MEDI4736 + AZD9150; A2: MEDI4736 + AZD5069; B1: (patients pre-treated with PD-L1 inhibitor) MEDI4736 + AZD9150; B2: (patients pre-treated with PD-L1 inhibitor) MEDI4736 + AZD5069; B3: (treatment naïve patients) MEDI4736 + AZD9150; B4: (treatment naïve patients) MEDI4736 + AZD5069; B5: AZD9150 until progression, followed by MEDI4736; B6: AZD5069 until progression, followed by MEDI4736; A3: MEDI4736 + AZD5069; A4: MEDI4736 + AZD9150 + tremelimumab; A5: MEDI4736 + AZD5069 + tremelimumab; A6: MEDI4736 + AZD9150; A7: MEDI4736 + AZD5069 | 147 | Recruiting | NA | NCT02499328 |
Advanced solid tumors | Phase 1 | Determine the number of patients with DLT, AE and serious AE; secondary outcomes: OS and ORR, assessed up to 2 years or until death | Arm 1: MEDI4736 Q2W; arm 2: MEDI4736 Q3W; arm 3 (dose expansion): MEDI4736 Q2W; arm 4: MEDI4736 Q4W; arm 5: MEDI4736 + tremelimumab Q4W | 264 | Recruiting | NA | NCT01938612 |
Solid tumors | Phase 1/Phase 2 | ORR assessed up to 10 years; secondary outcomes: clinical benefit rate assessed for 6 months, PFS and OS evaluated for up to 10 years | IPI on D1 + NIVO on D1, 15 and 29, course to be repeated every 42 days until unacceptable treatment related toxicity or progression of disease | 334 | Recruiting | NA | NCT02834013 (S1609 trial/DART trial) |
Refractory/recurrent solid tumors | Phase 1/Phase 2 | RR with IPI + NIVO combination therapy, RR with NIVO, MTD of NIVO, phase 2 dose of IPI + NIVO | IPI + NIVO | 352 | Recruiting | NA | NCT02304458 |
Metastatic/advanced solid tumors | Phase 1/Phase 2 RCT | OR rate; secondary outcomes: PFS, OS (time frame: 5 years) | Arm N: NIVO 3 mg/kg Q2W; arm N-I level 1: 4 doses of NIVO 1 mg/kg + IPI 1 mg/kg Q3W, later continued on monotherapy with NIVO 3 mg/kg Q2W; arm N-I level 2: 4 doses of IPI 3 mg/kg + NIVO 1 mg/kg Q3W, later on monotherapy with NIVO 3 mg/kg Q2W; arm N-I level 2b: 4 doses of IPI 1 mg/kg + NIVO 3 mg/kg Q3W, later on monotherapy with NIVO 3 mg/kg Q2W; arm N-I level 2c: IPI 1 mg/kg Q6W + NIVO 3 mg/kg Q3W; arm N-I level 2d: cobimetinib 60 mg/day for 21 days followed by 7 days off + IPI 1 mg/kg Q6W and NIVO 3 mg/kg Q3W | 1150 | Recruiting, results available for recurrent small cell lung cancer | Recurrent small cell lung cancer: ORR, disease control rate, SD, PR and progressive disease with NIVO (n = 40) noted in 18, 38, 20, 18 and 53% patients who received the drug, respectively; NIVO + IPI combination (n = 50) exhibited ORR of 17%, SD in 37%, PR in 15%, disease control rate of 54% and progressive disease in 37% patients | NCT01928394 [80] |