Phase II Study of Erdafitinib in Patients With Tumors With Fibroblast Growth Factor Receptor Mutations or Fusions: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol K2.

PURPOSE: Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions. METHODS: Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded. Enrolled subjects received oral erdafitinib at a starting dose of 8 mg daily continuously until intolerable toxicity or disease progression. The primary end point was objective response rate (ORR) with key secondary end points of safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the protocol. The median age was 61 years, and 52% of subjects had received ≥3 previous lines of therapy. The confirmed ORR was 16% (4 of 25 [90% CI, 5.7 to 33.0], P = .034 against the null rate of 5%). An additional seven patients experienced stable disease as best-confirmed response. Four patients had a prolonged PFS including two with recurrent WHO grade IV, IDH1-/2-wildtype glioblastoma. The median PFS and OS were 3.6 months and 11.0 months, respectively. Erdafitinib was manageable with no new safety signals. CONCLUSION: This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner.

Phase II Study of Erdafitinib in Patients With Tumors With FGFR Amplifications: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol K1.

PURPOSE: Despite fibroblast growth factor receptor (FGFR) inhibitors being approved in tumor types with select FGFR rearrangements or gene mutations, amplifications of FGFR represent the most common FGFR alteration across malignancies. Subprotocol K1 (EAY131-K1) of the National Cancer Institute-MATCH platform trial was designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 amplification. METHODS: EAY131-K1 was an open-label, single-arm, phase II study with central confirmation of presence of FGFR1-4 amplification in tumors. Patients with urothelial carcinoma were excluded. Enrolled patients received oral erdafitinib at a starting dose of 8 mg once daily continuously with escalation to 9 mg once daily continuously, on the basis of predefined time point assessments of phosphate levels, until disease progression or intolerable toxicity. The primary end point was centrally assessed objective response rate (ORR), with key secondary end points being 6-month progression-free survival (PFS6), PFS, overall survival (OS), and safety. RESULTS: Thirty-five patients were enrolled into this study with 18 included in the prespecified primary efficacy analysis. The median age of the 18 patients was 60 years, and 78% had received ≥3 previous lines of therapy. There were no confirmed responses to erdafitinib; however, five patients experienced stable disease (SD) as best response. One patient with an FGFR1-amplified breast cancer had a prolonged PFS >168 days (5.5 months). The median PFS was 1.7 months (90% CI, 1.1 to 1.8 months) and the median OS was 4.2 months (90% CI, 2.3 to 9.3 months). The estimated PFS6 rate was 13.8% (90% CI, 3.3 to 31.6). The majority of toxicities were grade 1 to 2 in nature, although there was one grade 5 treatment-related adverse event. CONCLUSION: Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. Our findings support that rearrangements and gene mutations, but not amplifications, of FGFR remain the established FGFR alterations with approved indications for FGFR inhibition.

Selection of and Response to Physical Activity-Based Social Comparisons in a Digital Environment: Series of Daily Assessment Studies.

BACKGROUND: Innovative approaches are needed to understand barriers to and facilitators of physical activity among insufficiently active adults. Although social comparison processes (ie, self-evaluations relative to others) are often used to motivate physical activity in digital environments, user preferences and responses to comparison information are poorly understood. OBJECTIVE: We used an iterative approach to better understand users' selection of comparison targets, how they interacted with their selected targets, and how they responded to these targets. METHODS: Across 3 studies, different samples of insufficiently active college students used the Fitbit system (Fitbit LLC) to track their steps per day as well as a separate, adaptive web platform each day for 7 to 9 days (N=112). The adaptive platform was designed with different layouts for each study; each allowed participants to select their preferred comparison target from various sets of options, view the desired amount of information about their selected target, and rate their physical activity motivation before and after viewing information about their selected target. Targets were presented as achieving physical activity at various levels below and above their own, which were accessed via the Fitbit system each day. We examined the types of comparison target selections, time spent viewing and number of elements viewed for each type of target, and day-level associations between comparison selections and physical activity outcomes (motivation and behavior). RESULTS: Study 1 (n=5) demonstrated that the new web platform could be used as intended and that participants' interactions with the platform (ie, the type of target selected, the time spent viewing the selected target's profile, and the number of profile elements viewed) varied across the days. Studies 2 (n=53) and 3 (n=54) replicated these findings; in both studies, age was positively associated with time spent viewing the selected target's profile and the number of profile elements viewed. Across all studies, upward targets (who had more steps per day than the participant) were selected more often than downward targets (who had fewer steps per day than the participant), although only a subset of either type of target selection was associated with benefits for physical activity motivation or behavior. CONCLUSIONS: Capturing physical activity-based social comparison preferences is feasible in an adaptive digital environment, and day-to-day differences in preferences for social comparison targets are associated with day-to-day changes in physical activity motivation and behavior. Findings show that participants only sometimes focus on the comparison opportunities that support their physical activity motivation or behavior, which helps explain previous, equivocal findings regarding the benefits of physical activity-based comparisons. Additional investigation of day-level determinants of comparison selections and responses is needed to fully understand how best to harness comparison processes in digital tools to promote physical activity.