Idelalisib for the treatment of indolent non-Hodgkin lymphoma: a review of its clinical potential

Figures & data

Table 1 Efficacy of idelalisib in clinical trials in iNHL

Study	Regimen	Population	Efficacy results
Phase I dose-ranging study^Citation37	IDELA 50–350 mg QD or BID continuously or intermittently (3 weeks on, 1 week off)	N=64 R/R iNHL; 97% had rituximab as prior therapy	ORR, 47% TTR, 1.3 mo DOR, 18.4 mo PFS, 7.6 mo
Phase I combination therapy study^Citation38	IDELA 150 mg BID + rituximab, B, or both	N=79 R/R iNHL; 58% were refractory to rituximab	ORR, 81% CR, 33% ORR for IDELA + R (75%), IDELA + B (88%), and IDELA + R + B (79%) DOR for IDELA + R (28.6 mo); not reached for IDELA + B or IDELA + R + B
Phase II monotherapy study^Citation3	IDELA 150 mg BID monotherapy	N=125 iNHL refractory to rituximab and an alkylating agent	ORR, 57% TTR, 1.9 mo DOR, 12.5 mo PFS, 11 mo

Abbreviations: B, bendamustine; BID, twice daily; CR, complete response; DOR, duration of response; IDELA, idelalisib; iNHL, indolent non-Hodgkin lymphoma; mo, months; ORR, objective response rate; PFS, progression-free survival; QD, once daily; R, rituximab; R/R, relapsed or refractory; TTR, time to response.

Table 2 Ongoing or planned idelalisib trials in iNHL

Study	Regimen	Population	Target accrual (status)/primary end point(s)
Phase I (NCT02457598)	Idelalisib + ONO/GS-4059; open label	Relapsed or refractory B-cell malignancies	N=138 (recruiting) Safety, toxicity, ORR
Phase I/II (NCT01306643)	Idelalisib monotherapy; open label	Previously treated iNHL	N=15 (recruiting) Safety, response rate
Phase II (NCT02439138)	Idelalisib monotherapy; open label	Previously treated Waldenström macroglobulinemia	N=30 (recruiting) ORR
Phase III (NCT01732913; Yosemite)	Idelalisib + rituximab; placebo controlled	Previously treated iNHL	N=375 (recruiting) PFS, response rate, OS
Phase III (NCT01732926; Bridalveil)	Idelalisib + bendamustine + rituximab; placebo controlled	Previously treated iNHL	N=450 (recruiting) PFS
Phase III (NCT02536300)	Idelalisib monotherapy	Previously treated follicular lymphoma or small lymphocytic lymphoma	N=240 (recruiting) Safety, ORR

Abbreviations: iNHL, indolent non-Hodgkin lymphoma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.

Table 3 Novel targeted therapies in development for iNHL

Agent (development phase in iNHL)	Therapeutic target
TGR-1202 (Phase I)	PI3Kδ
AMG 319 (Phase I)	PI3Kδ
IPI-145/duvelisib (Phase III)	PI3Kδ and PI3Kγ
BAY 80-6946/copanlisib (Phase III)	PI3Kα and PI3Kδ
ABT-199/venetoclax (Phase II)	BCL-2
ONO/GS-4059 (Phase I)	BTK
ACP-196/acalabrutinib (Phase I/II)	BTK

Abbreviations: BCL-2, B-cell lymphoma 2; BTK, Bruton’s tyrosine kinase; iNHL, indolent non-Hodgkin lymphoma; PI3K, phosphatidylinositol 3-kinase.

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