denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III
Hematology Disease Topics & Pathways:
Therapies, Combinations
Methods: CC-122-NHL-001 (NCT02417285) is an ongoing, open-label, phase 1b study of avadomide in combination with obinutuzumab conducted at 8 sites in 3 European countries with dose-escalation and dose-expansion parts in R/R FL. Eligible pts (age ≥18 y) had histologically confirmed, CD20-positive R/R NHL. Pts with FL (grade 1, 2, or 3a) had ≥1 prior standard regimen. Avadomide active ingredient in capsule (1.0–4.0 mg) or formulated capsules (3.0 or 4.0 mg) was administered orally once daily on days 1–5 followed by 2 days off (5/7-day schedule) every week of each 28-day cycle. Obinutuzumab 1000 mg was given intravenously on days 2, 8, and 15 of cycle 1 and on day 1 of cycles 2–8. Primary objectives were to determine the safety and tolerability of the combination, including the non-tolerated dose, maximum tolerated dose, and recommended phase 2 dose (RP2D). Response was assessed using Cheson 2007 criteria every 2 cycles to cycle 6, then every 3 cycles to cycle 12, and every 6 cycles thereafter. Median duration of response (mDOR) and median progression-free survival (mPFS) were assessed by Kaplan-Meier estimates.
Results: As of January 10, 2020, 73 pts with R/R NHL were enrolled and treated, including 19 with R/R diffuse large B-cell lymphoma, 1 with marginal zone lymphoma, and 53 with R/R FL; all 35 pts in the dose-expansion part of the study had R/R FL. The median age among treated pts was 61 y (range, 26–83), the median number of prior antilymphoma therapies was 3 (range 1–11), and 26 pts (36%) had prior autologous stem cell transplantation. As of July 14, 2020, tx was ongoing in 3/38 pts (8%) in dose-escalation (all ongoing in cycle >24, 1 pt ongoing in cycle >40). In the dose-expansion, tx was ongoing in 15/35 pts (43%); of these pts, all were ongoing in cycle >21 and 1 was ongoing in cycle 30. The RP2D of avadomide was established as 3.0 mg formulated capsule. In the expansion part of the study, pts received a median of 15 tx cycles (range, 1–33), and median tx duration was 60 wk (range, 1–132). The most common (≥10%) grade 3/4 TEAEs were neutropenia, reported in 19 pts (54%) and thrombocytopenia, reported in 7 pts (20%). Sixteen pts (46%) had a serious TEAE; only pyrexia (11%) and sepsis (9%) occurred in >2 pts. The objective response rate (ORR) among the 35 pts with R/R FL in the dose-expansion part of the study was 71%, including 40% with a complete response (CR). The mDOR was 14.6 mo (95% CI, 14.6–not estimable [NE]), and mPFS was 16.4 mo (95% CI, 8.3–NE). The median duration of PFS follow-up in dose-expansion was 14.4 mo (range, 0.8–30.3). Two pts had CRs lasting 13.7 mo and 15.3 mo before discontinuation owing to receiving allogeneic stem cell transplantation. Response rates were similar among all 53 R/R FL pts in both parts of the study (dose escalation and dose expansion) and in high-risk (ER and/or DR) FL pts (Table).
Conclusions: Long-term follow-up results demonstrate that avadomide plus obinutuzumab has a manageable safety profile and durable responses in patients with R/R FL. The antitumor activity of cereblon modulators plus next-generation anti-CD20 antibodies in heavily pretreated R/R NHL warrants further investigation as a novel chemotherapy-free option.
Disclosures: Michot: AstraZeneca: Other, Research Funding; Daiichi Sankyo: Research Funding; Eisai: Research Funding; Eos: Research Funding; Exelixis: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Forma: Research Funding; Lytix Biopharma: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Janssen: Other, Research Funding; AZD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundi Pharma: Other; Celgene: Other; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other; Xencor: Research Funding; Debiopharm: Research Funding; Abbvie: Research Funding; Agios: Research Funding; Amgen: Research Funding; Argen-x: Research Funding; Medimmune: Research Funding; Kyowa: Research Funding; Genentech: Research Funding; Lilly: Research Funding; Lysarc: Research Funding; Gustave Roussy: Honoraria, Other: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 bio, Research Funding. Doorduijn: Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Boccomini: SC Ematologia, ASOU Città della Salute e della Scienza di Torino, Turin, Italy: Current Employment. Kersten: Takeda: Research Funding; Miltenyi Biotech: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen/Cilag: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); MSD: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Kite/Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Chiappella: Servier: Honoraria; Takeda: Honoraria; Roche: Honoraria; Janssen: Honoraria; Gilead-Kite: Honoraria; Celgene: Honoraria; Iqone: Honoraria. Zinzani: Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Salles: Abbvie, Autolus, BMS/Celgene, Debiopharm, Genmab, Kite/Gilead, Epizyme, Janssen, Karyopharm, Morphosys, Novartis, F. Hoffmann-La Roche, Takeda: Consultancy; Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, Roche, Takeda: Other: Participation to educational events; Abbvie, Autolus, BMS/Celgene, Debiopharm, Genmab, Kite/Gilead, Epizyme, Janssen, Karyopharm, Morphosys, Novartis, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, F. Hoffmann-La Roche, Takeda: Honoraria. Hentrup: Neuronetics, Inc: Current equity holder in publicly-traded company, Ended employment in the past 24 months; BMS Consultant: Current Employment. Rhee: I own stocks for publicly-traded companies: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current Employment. Hagner: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Klein: Roche: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Pourdehnad: Celgene: Ended employment in the past 24 months, Patents & Royalties: Various CC-122 patents; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Various CC-122 patents. Hege: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Patents & Royalties: numerous, Research Funding; Celgene (acquired by Bristol Myers Squibb): Ended employment in the past 24 months; Mersana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Arcus Biosciences (Former Board of Directors): Divested equity in a private or publicly-traded company in the past 24 months. Dobmeyer: BMS: Consultancy. Nikolova: Celgene, A Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Ribrag: nanostring: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; gustave roussy comprehensive cancer center: Current Employment; servier: Consultancy; pharmamar: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; argenX: Research Funding; epizyme (EPZ): Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; EPZ: Honoraria, Membership on an entity's Board of Directors or advisory committees; AZD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other; Infinity: Honoraria, Membership on an entity's Board of Directors or advisory committees.
OffLabel Disclosure: This is a phase I study evaluating the safety and efficacy of avadomide in combination with obinutuzumab in patients with R/R B-cell NHL. Avadomide is an investigational agent and has not yet been approved in the US.