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. 2015 Oct 27;3(4):289–297. doi: 10.1093/gastro/gov053

Table 1.

Checkpoint inhibition in colorectal cancer: clinical trials

Author Trial phase Therapy Patient population Objective response rate Overall survival Progression-free survival Other findings
Le et al. [43] Phase II non-randomized, 3 centers Pembrolizumab (anti PD-1) 10 mg/kg IV every 14 days
  • Metastatic CRC, pre-treated with ≥2 regimens

  • Cohort A : MMR deficient CRC (11 patients)

  • Cohort B : MMR proficient CRC (21 patients)

  • Cohort A: 40% (4/10 patients)

  • Cohort B: 0% (0/18 patients)

  • Cohort A: Median OS not reached

  • Cohort B: Median OS - 5 months

  • Cohort A: Median PFS not reached

  • Cohort B: Median PFS – 2.2 months

High somatic mutation load associated with prolonged PFS (P = 0.02).
Topalian et al. [37] Phase I Nivolumab (anti PD-1) at doses of 1, 3, or 10 mg/kg every 2 weeks (in dose escalation phase) Heavily pre-treated, metastatic CRC (n = 17 patients) CR: 1 patient - - The only responding patient had deficient MMR and PD-L1 positive tumor
Brahmer et al. [44] Phase I BMS-936559 (anti PD-L1) at doses of 0.3, 1, 3, and 10 mg/kg on days 1, 15, and 29 of 6-week cycle Pre-treated, metastatic CRC (n = 18 patients) No objective responses - - -
Herbst et al. [40, 45] Phase I MPDL3280A (anti-PD-L1) at doses of≤1, 3, 10, 15 and 20 mg/kg IV every 3 weeks Pretreated CRC (n = 4 patients) PR: 1 patient - Ongoing response at 60 weeks Patient post-treatment after 48 weeks
Bendell et al. [46] Phase Ib
  • MPDL3280A (anti-PD-L1)

  • Arm A: MPDL3280A 20 mg/kg + bevacizumab 15 mg/kg every 3 weeks

  • Arm B: MPDL3280A 14 mg/kg + mFOLFOX6 + bevacizumab 10 mg/kg every 2 weeks

  • Arm A: Pretreated, metastatic CRC (≥3 prior regimens) (n = 14 patients)

  • Arm B: Oxaliplatin naïve metastatic CRC (n = 30 patients; 23/30 as first line therapy)

  • Arm A: 8% (1/13)

  • PR: 1 patient SD: 9 patients PD: 3 patients

  • Arm B: 40% (12/30)

  • PR: 12 patients SD: 14 patients PD: 4 patients

- For responders, PFS range 10–61 weeks Combinations well tolerated. No worsening of bevacizumab or chemotherapy-associated adverse events.
Chung et al. [55] Phase 2, single-arm, multicenter Tremelimumab (anti-CTLA-4) 15 mg/kg IV on day 1 of every 90-day cycle. Metastatic CRC, pretreated with any or combination of 5-FU, oxaliplatin, irinotecan and cetuximab (n = 47 patients)
  • PR : 1 patient

  • PD: 43 patients

4.8 months (95% CI, 4.1 to 7.7 months) PFS : 2.3 months (95% CI, 2.1–2.6 months) No clinically meaningful single-agent activity

CR = complete response; CRC = colorectal cancer; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; IV = intravenous; L1 = programmed death ligand 1; OS = overall survival; PD = progressive disease; PD-1 = programmed death 1; PD-MMR = mismatch repair; PFS = progression-free survival; PR = partial response; RR = response rate; SD = stable disease