POLATUZUMAB VEDOTIN PLUS BENDAMUSTINE AND RITUXIMAB OR OBINUTUZUMAB IN RELAPSED/REFRACTORY FL OR DLBCL: UPDATED RESULTS OF A PHASE 1B/2 STUDY

of ADCT-301 is currently enrolling patients (pts) with relapsed HL and NHL.Interim data are reported here.Methods: Relapsed/refractory HL or NHL pts who have no available established therapies known to provide clinical benefit at their current disease state are being recruited to a dose escalation (part 1) and dose expansion (part 2) phase I study.The primary objectives of part 1 are to assess the safety and tolerability and define a maximum tolerated dose (MTD) of ADCT-301 to recommend for part 2. The primary objective of part 2 will be to evaluate the safety and tolerability of ADCT-301 at this recommended dose.Efficacy (overall response rate, duration of response, progression-free survival, subtype-specific responses, and overall survival), pharmacokinetics, pharmacodynamics, and antidrug antibody activity are also being assessed.Patients receive IV infusions of ADCT-301 every 3 weeks (1 cycle) from a starting dose cohort at 3 μg/kg with subsequent cohorts enrolled at escalating doses according to a continual reassessment method.No intra-patient dose escalation is allowed.Results: As of 8 Feb 2017, 18 pts (11 male, 7 female; median age: 44 yrs [range 23-79]; median number of previous therapies: 4 [range 1-10]) with HL (n = 10) or NHL (n = 8) have been treated with ADCT-301 doses ranging from 3 to 45 μg/kg (median number of cycles: 2 [range 1-12]; median duration of treatment: 43 days [range 21-251]).A total of 4 pts have reported DLTs: 1 with maculopapular rash at 8 μg/kg; 1 with oral mucositis and small bowel enteritis at 20 μg/kg; 1 with elevated creatine phosphokinase at 30 μg/kg; and 1 with maculopapular rash and pruritus at 30 μg/kg.Treatment-emergent adverse events have been reported in 16 (88.9%)pts, including anemia (4 [22.2%] pts), pruritus (4 [22.2%] pts), and maculopapular rash (4 [22.2%] pts).The first disease responses were seen at 30 μg/kg: 1 HL pt achieved a complete response, and 1 HL pt achieved a partial response.A total of 6 pts achieved stable disease as their best response including 1 HL pt at 13 μg/kg who has remained progression-free for >30 weeks (>10 cycles).Conclusions: This dose escalation and expansion study will identify the MTD of ADCT-301 and provide a preliminary assessment of its singleagent anti-tumor activity and toxicity profile in R/R HL and NHL.Dose escalation (part 1) is continuing.Further initial safety, tolerability, and efficacy results are expected later this year.http://clinicaltrials.gov/