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Table 3 Phase 1 solid tumor trials investigating combined immunotherapy with anti-CTLA-4 plus anti- PD-1/PD-L1 monoclonal antibodies

From: Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC)

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 2 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]
  1. Abbreviations: MTD maximum tolerable dose, DLT dose limiting toxicity, SCCHN squamous cell carcinoma of the head and neck, RCT randomized controlled trial, NA not available, CI confidence interval, ORR overall response rate, OR objective response, OS overall survival, PFS progression free survival, RR response rate, RP2D recommended phase 2 dose, TRAE treatment related adverse events, NIVO nivolumab, IPI ipilimumab, PEMBRO pembrolizumab, MEDI4736 durvalumab, OD once daily dosing, BID twice daily, QID four times a day; Q(x)W, every (x) weeks, SD stable disease, PR partial response, D(x), day(x), AE adverse events