Previous studies have shown antitumor activity and a favorable safety profile with doublet combinations of obinutuzumab + polatuzumab vedotin or lenalidomide. An open-label, multicenter phase 1b/2 trial (GO29834; NCT02600897) was initiated to determine whether the triplet combination of obinutuzumab + polatuzumab vedotin + lenalidomide further increases antitumor responses in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Primary efficacy and safety analysis data from this phase 1b/2 study were presented at the 2019 ASH annual meeting.
Eligible patients had R/R FL (excluding grade 3b), had ≥1 bidimensionally measurable lesions ≥1.5 cm in their longest dimension, and had histologically documented CD20-positive cells. The 3 + 3 dose-escalation period defined the recommended phase 2 dose combination for polatuzumab vedotin + lenalidomide for the phase 2 expansion. Patients in the expansion cohort received induction treatment with 6 28-day cycles of obinutuzumab 1000 mg intravenously (IV; Cycle [C]1: Day [D] 1, D8, D15; C2-C6: D1); polatuzumab vedotin 1.4 mg/kg IV (D1), and lenalidomide 20 mg orally (D1-D21). Responders received maintenance treatment for 24 months (obinutuzumab 1000 mg on D1 every 2 months and lenalidomide 10 mg on D1-D21 during months 1-12). The primary end point was complete response (CR) at end of induction (EOI), as determined by the independent review committee (IRC) based on positron emission tomography–computed tomography scans.
A total of 56 patients from the phase 1b and phase 2 cohorts were enrolled and entered induction; the median duration of follow-up was 11.79 months. Baseline characteristics were median age, 62 years; male, 59%; Ann Arbor stage III to IV, 88%; Follicular Lymphoma International Prognostic Index (FLIPI)–high-risk (≥3), 55%; bulky disease (≥7 cm), 16%; ≥2 prior lines of therapy, 77%; refractory to last line of prior regimen, 59%; and refractory to any line of anti-CD20 treatment, 71%.
All patients had ≥1 adverse events (AEs), 32 (57%) had a serious AE, and 47 (84%) had a grade 3/4 AE. The most common grade 3 to grade 4 AEs were neutropenia (31 patients, 55%), thrombocytopenia (15 patients, 27%), infections (11 patients, 20%), and anemia (8 patients, 14%). AEs leading to a dose reduction or interruption of any drug occurred in 19 (34%) and 41 (73%) patients, respectively; the majority were modifications of lenalidomide. In addition, 17 (30%) patients had an AE that led to the discontinuation of any study drug.
A total of 46 patients were included in the primary efficacy population. The IRC-assessed modified Lugano objective response rate was 76%, including a CR rate of 65%. A subgroup analysis showed that CR was achieved by 68% (17/25) of patients who were refractory to their last treatment, by 71% of those that had received ≥3 lines of therapy, by 45% of patients with progression of disease within 2 years, and by 70% of FLIPI–high-risk patients. With a median follow-up duration of 15.1 months, median progression-free survival was not reached, and 83% of patients remained progression-free at 12 months.
The study investigators concluded that the novel triplet combination of obinutuzumab + polatuzumab vedotin + lenalidomide demonstrated a safety profile consistent with the known profiles of single-agent drugs and resulted in high CR rates at EOI in a heavily pretreated and refractory population.
Diefenbach C, et al. ASH Abstract 126. Session 623.