-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1839 Results of an Interim Safety Analysis of a Phase 2 Study of Daratumumab (Dara) Plus Cyclophosphamide, Bortezomib, and Dexamethasone ﴾CyBorD﴿ in Previously Untreated and Relapsed Patients ﴾Pts﴿ with Multiple Myeloma ﴾MM﴿

Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 9, 2017, 5:30 PM-7:30 PM
Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Habte Yimer, MD1, Jason Melear, MD2, Edward Faber3*, William I. Bensinger, MD4*, John M Burke, MD5, Sriya Gunawardena, MD6, Murphy Sean6*, Hollee Parros7*, Yana Lutska6*, Mohamed Darif, PhD8*, Anil Londhe, PhD8*, Ming Qi9*, Jon Ukropec6*, Thomas Lin6 and Robert M. Rifkin, MD10

1Texas Oncology - Tyler/ US Oncology Research, Tyler, TX
2Texas Oncology - Austin, Round Rock, TX
3Oncology Hematology Care, Inc., Cincinnati, OH
4Myeloma and Transplant Program, Swedish Cancer Institute, Seattle, WA
5Rocky Mountain Cancer Centers/US Oncology Research, Aurora, CO
6Janssen Scientific Affairs, LLC, Horsham, PA
7Janssen Research & Development, LLC, Horsham, PA
8Janssen Pharmaceuticals, Inc., Horsham, PA
9Janssen Research & Development, LLC, Spring House, PA
10US Oncology Research, Rocky Mountain Cancer Centers, Denver, CO

Background: Dara is a monoclonal anti‐CD38 antibody approved for the treatment of relapsed and refractory MM, but is associated with an infusion related reaction (IRR) rate of 46% for infusion 1 and 2% for infusion 2, and a median duration of infusions 1 and 2 of 7.0 and 4.3 hours, respectively (US Prescribing Information). CyBorD is a commonly used bortezomib based regimen for MM. This study was designed to evaluate Dara-CyBorD, as well as administration of the first Dara infusion as a divided dose over 2 days, in pts with MM who are previously untreated or have relapsed following only one line of therapy. We report results from a planned interim analysis of the first 48 pts who completed C1 of study treatment, focusing on the safety and IRR profile of Dara.

Methods: This is a multicenter, single-arm, open-label, Phase 2 study conducted at US community oncology centers. Key eligibility criteria include ≥ 18 years of age; documented MM per IMWG 2015 criteria; measurable MM; ECOG performance score of 0, 1, or 2; and no or one prior line of therapy. Approximately 100 pts will receive 4 to 8 28-day induction cycles of Dara-CyBorD, including oral cyclophosphamide 300 mg/m2 on Days 1, 8, 15, and 22; subcutaneous bortezomib 1.5 mg/m2 on Days 1, 8, and 15; and oral or IV dexamethasone 40 mg weekly. Dara is administered at a dose of 8 mg/kg IV on Days 1 and 2 of C1, then 16 mg/kg IV weekly from C1D8 through C2, then 16 mg/kg IV once every 2 weeks for C3-6, then 16 mg/kg IV once every 4 weeks for cycles 7-8. After completion of induction, pts may undergo an autologous stem cell transplant. All pts then receive 12 cycles of maintenance therapy with Dara 16 mg/kg IV every 4 weeks. Required pre-infusion medications are dexamethasone, acetaminophen, and diphenhydramine; montelukast is allowed at the investigator’s discretion.

Results: The first 48 pts completed 1 cycle of therapy with no discontinuations during C1. Median age was 62.5 (range 41-80) years, and 65% were male. Thirty-nine pts (81%) were previously untreated, and 9 pts (19%) had received 1 prior therapy. Forty-seven pts (98%) experienced at least 1 treatment emergent adverse event (TEAE) during C1, including 35 pts (73%) who experienced TEAE(s) attributed to Dara by the investigator. No grade 5 AE was reported during C1. The most commonly reported AEs during C1 were nausea (29%), fatigue (25%), diarrhea (23%), headache (17%), and chills (15%). Serious AEs (SAEs) occurred in 10% of pts during C1; no SAE was attributed to Dara by the investigator. IRRs occurred in 44% of pts, all grade ≤ 2, including 38% at C1D1 and 4% at C1D2. The most common IRRs were chills (13%), cough (6%), and nausea (6%). Respiratory IRRs occurred in 13% of pts, including cough (6%), dyspnea (4%), bronchospasm (2%), throat irritation (2%), and oropharyngeal pain (2%). The median infusion time was 4.3 hours for C1D1 and 3.5 hours for C1D2.

Conclusion: The overall safety profile during C1 of Dara-CyBorD was consistent with that previously reported for Dara with no new safety concerns. Administration of the first Dara infusion as a split dose of 8 mg/kg/day over 2 days resulted in a similar IRR rate and a shorter median infusion time for C1D1 than the US prescribing information for single dose. No grade ≥ 3 IRRs were observed. These findings demonstrate that splitting of the first Dara infusion in the community setting is feasible, results in a similar IRR rate with no observed grade ≥ 3 IRRs, and reduces the median time for the first Dara infusion.

Disclosures: Yimer: Bellucum Pharma: Equity Ownership; Juno pharma: Equity Ownership. Melear: Janssen: Membership on an entity's Board of Directors or advisory committees. Faber: Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Aventis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bensinger: Janssen: Membership on an entity's Board of Directors or advisory committees. Burke: Incyte: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Celgene: Consultancy, Other: Travel grant; Gilead: Consultancy. Gunawardena: Janssen: Employment. Sean: Janssen: Employment, Equity Ownership. Parros: Janssen: Employment. Lutska: Janssen: Employment. Darif: Janssen: Employment, Equity Ownership. Londhe: Janssen: Employment, Equity Ownership. Qi: Johnson & Johnson, LLC: Equity Ownership; Janssen: Employment. Ukropec: Janssen: Employment. Lin: Janssen: Employment. Rifkin: McKesson Specialty Health: Employment; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH