Table 2.

Information about doses and important toxicities present in later trials and correlation with early phase I trials

IpilimumabNivolumabPembrolizumabAtezolizumabAvelumabDurvalumabIpilimumab + nivolumab
Dose used in later trial (% of RP2D from phase I)3 mg/kg q3wks (400%)3 mg/kg q2wks (no RP2D)Different doses (66%–333%)1,200 mg q3wks (100%)10 mg/kg q2wks (50%)10 mg/kg q2wks (100%)Nivolumab 1 mg/kg Ipilimumab 3 mg/kg
 q3wks × 4 doses (100%)
Number of patients in phase I triala1920730171272786
Number of patients in later trialsb1371,9041,3341,160337191314
Number of types of clinically significant toxicities in later trialsc518216645
Number of types of toxicities described in phase I trial (% of types of toxicities described in later trials)2 (40)7 (39)6 (29)3 (50)4 (67)1 (25)5 (100)
Number of types of immune-related toxicities in later trialsc79154877
Number of types of immune-related toxicities described in phase I trials (% of types of immune-related toxicities described in later trials)3 (42.9)6 (66.7)4 (26.6)3 (75)3 (37.5)3 (43)7 (100)
Treatment-related mortality in phase I trials (% of patients in the trials)003.330000
All trials = 0.18%
Treatment-related mortality later trials (% of patients in the trials)2.90.320.3700.31.050
All trials = 0.33%
  • Abbreviations: DLTs, dose-limiting toxicities; q2wks, every 2 weeks; q3wks, every 3 weeks; RP2D, recommended phase II dose.

  • aPatients included during dose-escalation and dose-expansion cohorts for dose-finding purposes only.

  • bData obtained from all later trials for the different FDA-approved indications.

  • cClinically significant toxicities were defined as treatment-related toxicities leading to death, treatment delays and discontinuations, and toxicities among the three most frequent grade 3/4 laboratory and non-laboratory toxicities with an overall incidence of at least 1% (33); in the case of immune-related toxicities, all types of toxicities were included regardless of grade.