Based on in vitro studies, Polatuzumab vedotin + Obinutuzumab + Venetoclax ( Pola-G-Ven )may have significant anti-tumor activity in relapsed / refractory follicular lymphoma ( R/R FL ).
Researchers have reported a pre-planned interim analysis of the safety / efficacy of induction treatment with Pola-G-Ven in pateints with R/R follicular lymphoma in a phase Ib/II study.
The aim of the study was to assess the safety and efficacy of induction and maintenance with Pola-G-Ven in patients with R/R follicular lymphoma.
The open-label, multicenter, single arm study has included patients with R/R follicular lymphoma ( excluding grade 3b ) who have received greater than or equal to 1 prior anti-CD20 antibody-containing chemo-immunotherapy regimen.
The study included an initial 3+3 dose-escalation ( DE ) phase ( to determine the recommended phase II dose [ RP2D ] of both Polatuzumab vedotin and Venetoclax ) followed by an expansion phase at the RP2D of Pola-G-Ven.
Patients received induction treatment with 6 x 21-day ( D ) cycles ( C ) of: Obinutuzumab 1000mg intravenous ( IV ) ( C1: D1, D8, D15; C2–6: D1 ); Polatuzumab vedotin 1.4mg/kg or 1.8mg/kg ( DE ) or RP2D ( expansion ) IV ( D1 ); and Venetoclax 200-800mg ( DE ) or RP2D ( expansion ) orally ( PO ) daily.
Patients with complete response ( CR ) / partial response ( PR ) / stable disease ( SD ) at the end of induction ( EOI ) received Obinutuzumab 1000mg ( D1 every 2 months, for 24 months ), and Venetoclax ( RP2D daily, for 8 months ).
Primary endpoints were C1 dose-limiting toxicities ( DLTs ), safety / tolerability, CR rate at EOI ( modified Lugano criteria ).
At the interim data cut-off ( 13 Nov 2019 ), 71 patients were enrolled. Median patient age was 63 ( range 36–78 ) years; 55% were male; 49% had Follicular Lymphoma International Prognostic Index ( FLIPI ) 3-5; 73% had received greater than or equal to 2 prior therapy lines; 52% were refractory to their last treatment; 16% had bulky disease ( greater than or equal to 7cm ).
Following the initial DE, the combination of Polatuzumab vedotin 1.8mg/kg + Ven 800mg was selected as the RP2D for expansion.
The most common all grade non-hematologic adverse events were infections, diarrhea, nausea, and fatigue. Grade 3/4 adverse effects were reported in 59% of patients, most commonly: neutropenia ( 31% ), thrombocytopenia ( 18% ), infections ( 13% ), and anemia ( 6% ).
Peripheral neuropathy was reported in 41% of patients, all were grade 1 or 2; 4 patients required a dose reduction of Pola and 2 patients discontinued Polatuzumab vedotin due to peripheral neuropathy.
Adverse effects leading to Venetoclax dose reduction or interruption occurred in 30% and 47% of patients, respectively, with the most common cause being cytopenias.
Preliminary efficacy data for this interim analysis of 15 efficacy evaluable patients showed an independent review committee-assessed modified Lugano criteria response rate of 87% and a CR rate of 60%.
Fourteen patients continue on maintenance treatment.
With a median follow-up duration of 7.4 months in the efficacy-evaluable population, median progression-free survival was not reached.
In conclusion, the safety profile of Polatuzumab vedotin - Obinutuzumab - Ven is consistent with known profiles of the individual drugs.
Response rates at EOI with Pola-G-Ven are promising, with high complete response compared with available R/R FL treatments. ( Xagena )
Source: EHA25 - European Hematology Association Virtual Meeting, 2020