Background: Older adults (aged 65 and above) with advanced cancers are underrepresented in clinical trials particularly early phase clinical trials. To assess their participation and clinical response on phase I treatment, we analyzed the characteristics of such patients treated on phase I trials with an emphasis on comparison b/w middle age and adolescent/young adults (AYA). Methods: In total, 1489 consecutive patients treated on phase I trials b/w Dec 2004-July 2013 were separated into 3 age-based cohorts: AYA (15-39y), middle age (40-64y), elderly (65+y) and analyzed for clinical characteristics and response outcomes per RECIST. The clinical benefit (defined as a response of SD ≥ 6 months, PR, or CR, per RECIST) was determined for each cohort. We calculated the odds ratios of achieving a favorable clinical benefit for the 3 age cohorts, and for elderly and AYA in comparison to the middle age. Results: Of 1489 treated patients, 278 were elderly (18%, median age 68.9y), 220 AYA (15%, median age 32.6y), 991 middle age (67%, median age 53.8y). The median number of prior therapies was 3 in all three age groups and the most common malignancies were gastrointestinal (n = 438, 29%), gynecologic (n = 234, 16%), and thoracic/head/neck (n = 216, 15%). Median time on trial did not vary significantly between the 3 age cohorts (3 months in elderly, 3.5 months in middle age, 3.3 months in AYA). The odds ratio of achieving clinical benefit in elderly vs middle age is 1.10, p 0.19 (two-tailed), p 0.09 (one-tailed). Similarly the odds ratio of achieving clinical benefit in AYA vs middle age is 0.85, p 0.31 (proportions z-test, two tailed), p 0.15 (one-tailed). No significant differences were found in the odds ratio of response between the elderly, AYA and middle age cohorts. Analysis of the incidence of toxicities among the three age cohorts is in progress. Conclusions: Elderly patients accounted for less than 20% of patients on phase I clinical trials but those who participated were just as likely to achieve a clinical benefit as the AYA and middle age patients. Participation in phase I therapy may offer a reasonable therapeutic option for elderly patients with advanced cancers.