Updated Organ Response Results of an Open-Label Study to Evaluate the Safety and Tolerability of Cael-101 in Patients with AL Amyloidosis Receiving Anti-Plasma Cell Therapy
Authors: Valent Jason , Silowsky John , Kurman Michael R. , Daniel Eileen , Jobes Janet , Harnett Mark , Fada Sherry , Spector Michael , Stefunek Kathleen , Staley Heather , Schlueter Kristen , Samaras Christy J. , Anwer Faiz , Khouri Jack , Zonder Jeffrey A. , Liedtke Michaela , Sobolov Susan B. 
Published: November 2021

Abstract
Background: CAEL-101 is an IgG1 monoclonal antibody intended to enable immune clearance of AL amyloid deposits. This study (NCT04304144) data allowed dose selection of CAEL-101 for the ongoing Phase 3 studies in patients with Mayo stage IIIa and IIIb AL amyloidosis cardiomyopathy newly diagnosed and treated with bortezomib, cyclophosphamide, and dexamethasone (CyBorD) alone or in combination with daratumumab.
Methods: 13 patients were treated with CAEL-101 and CyBorD and an additional 5 patients were treated with CAEL-101, daratumumab, and CyBorD. Organ response data on assessable patients were evaluated per consensus criteria as per institutional standard of care. Safety, pharmacokinetic and anti-drug antibody data will be reported separately.
Results: The follow up for patients receiving CAEL-101 and CyBorD is 12 to 15 months and for the CAEL-101, Daratumumab, and CyBorD is 4 to 6 months. 16 of 18 patients remain on treatment. One discontinuation was due to death from E. coli sepsis and the other due to lack of hematologic response with deterioration of heart function requiring heart transplant after only 6 doses of CAEL-101. Organ response in cardiac patients by NT pro BNP criteria occurred in 4 of 8 evaluable patients treated with CAEL-101 and CyBorD (time to organ response range 2 - 12 months) and in 2 of 3 patients treated with CAEL-101, daratumumab, and CyBorD (time to organ response range 3 - 5 months). Four patients have had repeat echocardiogram 1 year from start of CAEL-101 based therapy with interpretable global peak longitudinal strain (GLS). The GLS improved in 2 patients by -5% (-6.4% to -11.4%) and -5.1% (-12.8% to -17.9%). GLS remained stable in the other 2 patients. All 9 patients with evaluable kidney involvement by 24 hour urine protein achieved an organ response. Responses occurred in as little as 2 months in 5 patients (range 2 - 7 months). The time to organ response were similar in the daratumumab and non-daratumumab treated patients. One patient with hematologic stable disease and persistent 71% improvement in 24 hour urine protein at 10 months from start of CAEL-101 based therapy is most notable.
Conclusions: CAEL-101 with anti-plasma cell therapy remains reasonably well tolerated with no unanticipated adverse effects. Organ responses, most notably renal response, have occurred early in the course of therapy and appears to be durable. Organ responses in some patients have also improved over time with some significant improvement in patient GLS evaluations by echocardiogram. These results encourage clinical trial participation in the ongoing CAEL-101 clinical trials in Mayo stage IIIa and IIIb AL amyloidosis patients.

Disclosures
Valent: Celgene Corporation: Speakers Bureau; Amgen: Speakers Bureau; Caelum Biosciences: Other: Clinical Trial Funding; Takeda Pharmaceuticals: Speakers Bureau. Silowsky: Caelum Biosciences: Current Employment. Kurman: Caelum Biosciences: Other: Medical Monitor. Daniel: Caelum Biosciences: Current Employment. Jobes: Caelum Biosciences: Current Employment. Harnett: Caelum Biosciences: Current Employment. Spector: Caelum Biosciences: Current Employment. Anwer: GlaxoSmithKline: Research Funding; Allogene Therapeutics: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding. Zonder: BMS: Consultancy, Research Funding; Janssen: Consultancy; Caelum Biosciences: Consultancy; Intellia: Consultancy; Regeneron: Consultancy; Amgen: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy. Liedtke: Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trial Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Sobolov: Caelum Biosciences: Current Employment.

OffLabel Disclosure:
CAEL-101 is a monoclonal antibody directed at AL amyloid deposits. The purpose is to promote immune clearance of amyloid deposits.