The Adaptive phase (ph) 1/2 trial design with larger-sized expansion cohorts (ExC) (abbreviated, ‘SUMO’ design) has gained popularity in oncology. We examined the perceptions of ph 1 investigators toward this design.
Subjects were identified by expert nomination or via PubMed search of authors who have published > 3 ph1 or ph 1/2 cancer drug trials from 2010-17. Invitations were sent by emails containing an e-link to a survey with 4 domains: (1) ph 1 experience; (2) perception on utility, (3) safety & scientific validity, & (4) operational challenges. Responses were graded as Likert scores.
534 invitations were sent & 98 responses (18.3%) were returned. Of the 80 respondents who completed all questions, 76.5% are male & 92.8% are academic physicians in university teaching hospitals from North America (31.7%), Asia (30.5%), Europe (25.6%) & Australia (12.2%). They are mainly experienced principal investigators (PI): 70% are PI of > 5 active ph 1 trials, 60% have been PI for > 10 yrs, 53% graduated > 20yrs. Over 80% felt that SUMO design can expedite drug development, but opinions are divided over if it should be preferred over other designs (46.3% Yes, vs 53.7% otherwise, o/w). When selecting ExC, 57.1% felt that strong scientific rationale based on preclinical data is the key, but 31.2% felt it was not necessary. Divergent opinions are reported over the appropriateness of waiving standard statistical methods like pre-defining type 1/2 error (45.5% OK to waive, vs 54.5% o/w), early stopping rule (52% OK to waive, vs 48% o/w) & a ‘control arm’ (26.7% OK to waive vs 73.3% o/w) in randomized cohorts. Most respondents (68%) felt that the SUMO design for first-in-human trials does not put patients at greater risk. Most agreed with increasing size & number of ExC, yet, 74.7% reported ‘some’ to ’significant’ operational challenges at their respective institutions with SUMO trials. Detailed correlations will be presented.
Although the SUMO design is perceived to be a safe & efficient way to develop cancer drugs by most experienced Ph 1 trialists, this survey has highlighted some pressing issues in its application: the need to optimize the scientific & statistical justification of ExCo selection, to recognize & improve the operational challenges posed by such design.
Clinical trial identification
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All authors have declared no conflicts of interest.