Background:

CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host's immune response. The high affinity CD47 blocker fusion protein, ALX148, is linked to an inactive immunoglobulin Fc region to minimize toxicity. ALX148 is half the size of an antibody, has been well tolerated, and enhances the innate and adaptive immune response against cancer in combination with anticancer therapeutics across solid and hematologic tumors (ASCO 2020 #3056, EHA 2020 #EP1247). Characterization of ALX148's tolerability profile and antitumor activity in combination with rituximab are reported in patients (pts) with non-Hodgkin Lymphoma (NHL).

Methods:

Patients with relapsed or refractory CD20-positive B-cell NHL for which no curative therapy was available received ALX148 (10 mg/kg QW or 15 mg/kg QW) in combination with rituximab (375 mg/m2 weekly for 4 doses followed by once monthly for 8 doses). The primary endpoint for the safety population was dose limiting toxicity (DLT). Tumor response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed in all pts. Data are reported as of 30Jun2020 in these fully enrolled cohorts with final data to be updated at the time of presentation.

Results:

A total of 33 patients with NHL were administered ALX148 in combination with rituximab. Twenty-two pts with median age of 66 years (range 32-80) were administered ALX148, 10 mg/kg QW (ALX10), in combination with rituximab [DLBCL, n=11; mantle cell lymphoma (MCL), n=4; follicular lymphoma (FL), n=5; and marginal zone lymphoma (MZL), n=2]. Eleven pts with median age of 64 years (range 53-78) were administered ALX148, 15 mg/kg QW (ALX15), in combination with rituximab (DLBCL, n=6; MCL, n=1; FL, n=3; and MZL, n=1). There have been no DLTs reported in the fully enrolled safety cohorts, and the MTD of ALX148 in combination with rituximab has not been reached. The maximum ALX148 administered dose is 15 mg/kg QW. Twenty-eight pts experienced any AE, while 16 pts reported mostly low grade treatment-related adverse events (TRAE). The most common TRAEs were rash (21%, n=7), fatigue (9%, n=3), anemia, nausea, neutropenia, and pruritus (6%, n=2 each). With a median follow up of 14 months, objective responses were observed across all histologies in response-evaluable ALX10 pts: 40.9% ORR (4CR,5PR, 6SD, n=22 total) and with a median follow up of 9 months in ALX15 pts: 63.6% ORR (3CR, 4PR, 1SD, n=11 total). Preliminary results indicate favorable ALX148 PK and near complete CD47 receptor occupancy across the dosing interval. Final results will be updated at time of presentation.

Conclusions:

ALX148 demonstrates excellent tolerability with durable responses in combination with rituximab in patients with relapsed/refractory NHL. The MTD of ALX148 in combination with rituximab was not reached. Encouraging preliminary activity and favorable PK/PD characteristics in combination with rituximab were observed at all dose levels with greater objective response rates reported at the MAD of 15 mg/kg QW.

Disclosures

Kim:Boryung: Consultancy; Voronoi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Takeda: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; AstraZeneca: Consultancy. Lakhani:incyte: Research Funding; merck: Research Funding; mersana: Research Funding; northern biologics: Research Funding; odonate: Research Funding; pfizer: Research Funding; ikena: Research Funding; symphogen: Research Funding; taiRx: Research Funding; tesaro: Research Funding; livzon: Research Funding; loxo: Research Funding; macrogenics: Research Funding; inhibRx: Research Funding; cytomx: Research Funding; formation biologics: Research Funding; forty seven inc: Research Funding; alexion Pharmaceuticals: Research Funding; Alpine Biosciences: Research Funding; ALX Oncology Inc.: Research Funding; Apexian: Research Funding; asana biosciences: Research Funding; ascentage pharma: Research Funding; beigene: Research Funding; celgene: Research Funding; cerulean pharma: Research Funding; constellation pharma: Research Funding; coordination therapeutics: Research Funding; regeneron: Research Funding; sapience therapeutics: Research Funding; shattuck labs: Research Funding; innovent bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; jounce therapeutics: Research Funding. Gainor:theravance: Consultancy; adaptimmune: Research Funding; ariad: Research Funding; astrazeneka: Research Funding; blueprint medicines: Research Funding; lily: Consultancy; gilead sciences: Consultancy; merck: Consultancy, Research Funding; moderna therapeutics: Consultancy, Research Funding; tesaro: Research Funding; blueprint medicines: Consultancy; novartis: Research Funding; oncorus: Consultancy; regeneron: Consultancy; bristol-myers Squibb: Consultancy, Research Funding; amgen: Consultancy; array biopharma: Consultancy, Research Funding; agios: Consultancy; ironwood pharmaceuticals: Consultancy; takeda: Consultancy; genentech: Consultancy, Research Funding; jounce therapeutics: Consultancy, Research Funding. Kamdar:Roche: Research Funding. Fanning:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Squifflet:ALX Oncology Inc.: Consultancy; IDDI: Current Employment. Jin:ALX Oncology Inc.: Current Employment. Forgie:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company; Pfizer Inc.: Ended employment in the past 24 months. Wan:Tallac Therapeutics: Current Employment, Current equity holder in private company; ALX Oncology Inc.: Consultancy, Current equity holder in publicly-traded company. Pons:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Randolph:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Kim:F. Hoffmann-La Roche: Research Funding; Pfizer: Research Funding; JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2020 by The American Society of Hematology
2020
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