• Based on a recent planned review, the Data Monitoring Committee (DMC) rec­om­mends Phase Ib/II study of dara­tu­mu­mab plus atezo­lizu­mab (anti PD-L1 anti­body) in patients with pre­vi­ously treated non-small cell lung cancer to be terminated.
• Phase I MMY2036 study of dara­tu­mu­mab plus JNJ-63723283 (anti PD-1 anti­body) in patients with multiple myeloma, dis­con­tinued
• Health Authorities have been informed about these events and Janssen has contacted its partner com­panies conducting dara­tu­mu­mab and anti-PD-(L)1 com­bi­na­tion studies to discuss ceasing enrollment and dosing of the com­bi­na­tion while the data is being further in­ves­ti­gated

Copenhagen, Denmark (Press Release) – Genmab A/S (Nasdaq Copenhagen: GEN) announced today that fol­low­ing a planned review, the DMC has rec­om­mended that the Phase Ib/II study (CALLISTO/LUC2001) of dara­tu­mu­mab in com­bi­na­tion with atezo­lizu­mab versus atezo­lizu­mab mono­therapy in patients with previ­ously treated ad­vanced or metastatic non-small cell lung cancer should be terminated. In addi­tion the phase I MMY2036 study of dara­tu­mu­mab plus JNJ-63723283, an anti PD-1 anti­body in patients with multiple myeloma will be dis­con­tinued.

The DMC de­ter­mined that there was no observed benefit within the combi­na­tion treat­ment arm, dara­tu­mu­mab plus atezo­lizumab, over atezo­lizumab mono­­therapy, and rec­om­mended termination of the study. In addi­tion to the lack of benefit, the DMC noted a numerical in­­crease in mortality-related events in the combi­na­tion arm.

Based on these findings, Janssen has made the de­ci­sion also to dis­con­tinue the MMY2036 study, which was eval­u­ating a com­bi­na­tion of dara­tumumab and anti-PD-1 (JNJ-63723283) in patients with multiple myeloma. Janssen has informed Health Authorities about these events and has contacted its partner com­pa­nies conducting dara­tumumab and anti-PD-(L)1 com­bi­na­tion studies to discuss ceasing enrollment and dosing of the com­bi­na­tion while the data is being further in­ves­ti­gated.

In August 2012, Genmab granted Janssen an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab.

“While we are disappointed that the studies will be dis­con­tinued, Genmab fully sup­ports Janssen’s de­ci­sion as patient safety is paramount in drug devel­op­ment. We look for­ward to gaining a better under­stand­ing of the data upon further analysis. We are pleased that the develop­ment pro­gram for dara­tumumab remains expansive and con­tinues to benefit patients with multiple myeloma” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the LUC2001 study

This ran­domized, multi­center, Phase Ib/II study in­cludes 98 patients with pre­vi­ously treated ad­vanced or metastatic NSCLC. Patients will be ran­domized to receive dara­tu­mu­mab at 16 milligrams per kilo­gram (mg/kg) weekly for 3 cycles and on day 1 of every 21-day cycle there­after. Atezolizumab will be admin­is­tered at 1,200 mg on day 2 of Cycle 1 and on day 1 of every 21-day cycle there­after. Patients will con­tinue to receive treat­ment until disease pro­gres­sion or unacceptable toxicity. Patients in the atezo­lizu­mab mono­therapy arm with con­firmed disease pro­gres­sion will be eli­gible to crossover to the dara­tu­mu­mab plus atezo­lizu­mab arm, if they meet the crossover eligibility criteria. The pri­mary end­point of the study is per­cent­age of patients with ORR, defined as per­cent­age of patients with PR or CR as defined by Response Evaluation Criteria in Solid Tumors (RECIST).

About MMY2036 study

This ran­domized, multi­center, multiphase study in­cludes up to 386 patients with re­lapsed or refractory multiple myeloma. Approximately 6 subjects will be enrolled in Part 1 (a safety run-in cohort) followed by 80 subjects ran­domly assigned in a 1:1 ratio to the 2 treat­ment arms in Part 2 (Phase 2). After all subjects in Part 2 are followed-up for approx­i­mately 4 months, it will be de­ter­mined, based on review of all avail­able data, whether to ini­ti­ate Part 3 (Phase 3) of this study, where an addi­tional 300 subjects will be ran­domly assigned in a 1:1 ratio to the 2 treat­ment arms. Patients are ran­domized to receive JNJ 63723283 (PD-1 anti­body) admin­is­tered in com­bi­na­tion with dara­tu­mu­mab, com­pared with dara­tu­mu­mab alone. Dara­tu­mu­mab is dosed at 16 milligrams per kilo (mg/kg) weekly for 8 weeks, then once every other week for 16 weeks; then once every 4 weeks. JNJ 63723283 is dosed at 240 milligrams IV fixed dose during week 1 on cycle 1 (28 days) day 2, cycle 1 day 15, then every 2 weeks there­after. The pri­mary end­points of the study are in Part 1: number of par­tic­i­pants with adverse events (AE) Including Dose-Limiting Toxicities (DLTs) during cycle 1. An adverse event is any untoward medical occurrence in par­tic­i­pant who received study drug without regard to possibility of causal rela­tion­ship. In Part 2: Overall Response Rate (ORR) as per Inter­national Myeloma Work­ing Group (IMWG) criteria and in Part 3: Progression-Free Survival (PFS) which is the time from treat­ment start until the disease get worse.

About DARZALEX® (dara­tu­mu­mab)

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous in­fusion is indicated in the United States in combi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant; in combi­nation with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy; in com­bi­na­tion with poma­lido­mide and dexa­metha­sone for the treat­ment of patients with multiple myeloma who have received at least two prior ther­a­pies, in­­clud­ing lena­lido­mide and a protea­some inhibitor (PI); and as a mono­therapy for the treat­ment of patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a PI and an immuno­modu­latory agent, or who are double-refractory to a PI and an immuno­modu­latory agent.¹ DARZALEX is the first mono­clonal anti­body (mAb) to receive U.S. Food and Drug Admin­istra­tion (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use in com­bi­na­tion with lena­lido­mide and dexa­metha­sone, or bor­tez­o­mib and dexa­meth­a­sone, for the treat­ment of adult patients with multiple myeloma who have received at least one prior ther­apy and as mono­therapy for the treat­ment of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a PI and an immuno­mo­du­latory agent and who have dem­onstrated disease pro­gres­sion on the last ther­apy. In Japan, DARZALEX is approved in com­bi­na­tion with lena­lido­mide and dexa­metha­sone, or bortezo­mib and dexa­metha­sone, for treat­ment of adults with re­lapsed or refractory multiple myeloma. DARZALEX is the first human CD38 mono­clonal anti­body to reach the mar­ket. For more in­­for­ma­tion, visit www.DARZALEX.com.

Daratumumab is a human IgG1k mono­clonal anti­body (mAb) that binds with high affinity to the CD38 molecule, which is highly ex­pressed on the surface of multiple myeloma cells. Dara­tu­mu­mab triggers a person’s own immune sys­tem to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mech­a­nisms of action and through immuno­modu­latory effects, in addi­tion to direct tumor cell death, via apop­tosis (programmed cell death).^1,2,3,4,5

Daratumumab is being devel­oped by Janssen Biotech, Inc. under an exclusive world­wide license to devel­op, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab from Genmab. A com­pre­hen­sive clin­i­cal develop­ment pro­gram for dara­tumumab is ongoing, in­­clud­ing multiple Phase III studies in smol­der­ing, re­lapsed and frontline multiple myeloma settings and in amy­loid­osis. Additional studies are ongoing or planned to assess the poten­tial of dara­tu­mu­mab in other malignant and pre-malignant diseases, such as NKT-cell lym­phoma, myelo­dys­plastic syn­dromes, B and T-ALL. Dara­tu­mu­mab has received two Break­through Therapy Desig­nations from the U.S. FDA, for multiple myeloma, as both a mono­therapy and in com­bi­na­tion with other ther­a­pies.

About Genmab

Genmab is a publicly traded, inter­na­tional bio­technology com­pany specializing in the creation and develop­ment of dif­fer­en­ti­ated anti­body thera­peutics for the treat­ment of cancer. Founded in 1999, the com­pany has two approved anti­bodies, DARZALEX® (dara­tu­mu­mab) for the treat­ment of certain multiple myeloma indi­ca­tions, and Arzerra® (ofatumumab) for the treat­ment of certain chronic lym­pho­cytic leukemia indi­ca­tions. Dara­tu­mu­mab is in clin­i­cal devel­op­ment for addi­tional multiple myeloma indi­ca­tions, other blood cancers, and solid tumors. A sub­cu­tane­ous for­mu­la­tion of ofatumumab is in devel­op­ment for relapsing multiple sclerosis. Genmab also has a broad clin­i­cal and pre-clinical prod­uct pipe­line. Genmab's tech­nology base consists of val­i­dated and pro­pri­e­tary next generation anti­body tech­nolo­gies - the DuoBody® plat­form for generation of bispecific anti­bodies, and the HexaBody® plat­form which creates effector function en­hanced anti­bodies. The com­pany in­tends to leverage these tech­nolo­gies to create oppor­tu­ni­ties for full or co-ownership of future prod­ucts. Genmab has alliances with top tier pharma­ceu­tical and bio­tech­nology com­panies. For more in­­for­ma­tion visit www.genmab.com.

This Company Announcement con­tains for­ward looking state­ments. The words “believe”, “expect”, “antici­pate”, “intend” and “plan” and similar ex­pres­sions identify for­ward looking state­ments. Actual results or per­for­mance may differ ma­teri­ally from any future results or per­for­mance ex­pressed or implied by such state­ments. The im­por­tant factors that could cause our actual results or per­for­mance to differ ma­teri­ally in­clude, among others, risks associ­ated with pre-clinical and clin­i­cal devel­op­ment of prod­ucts, un­cer­tain­ties related to the out­come and conduct of clin­i­cal trials in­­clud­ing un­fore­seen safety issues, un­cer­tain­ties related to prod­uct manu­fac­tur­ing, the lack of mar­ket acceptance of our prod­ucts, our in­abil­ity to man­age growth, the competitive en­viron­ment in rela­tion­ to our business area and mar­kets, our in­abil­ity to attract and retain suitably qualified per­son­nel, the un­en­force­ability or lack of protection of our patents and pro­pri­e­tary rights, our rela­tion­ships with affiliated entities, changes and devel­op­ments in tech­nology which may render our prod­ucts obsolete, and other factors. For a further discussion of these risks, please refer to the risk man­age­ment sections in Genmab’s most recent financial reports, which are avail­able on www.genmab.com. Genmab does not under­take any obli­ga­tion to update or revise for­ward looking state­ments in this Company Announcement nor to con­firm such state­ments to reflect sub­se­quent events or cir­cum­stances after the date made or in rela­tion­ to actual results, unless required by law.

Genmab A/S and/or its sub­sid­i­aries own the fol­low­ing trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in com­bi­na­tion with the Y-shaped Genmab logo®; HuMax®; DuoBody®; DuoBody in com­bi­na­tion with the DuoBody logo®; HexaBody®; HexaBody in com­bi­na­tion with the HexaBody logo®; and UniBody®. Arzerra® is a trademark of Novartis AG or its affiliates. DARZALEX® is a trademark of Janssen Pharma­ceutica NV.

References

1. DARZALEX Prescribing information, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed May 2018
2. De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.
3. Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.
4. Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.
5. Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012; 120(21): abstract 2974.

Source: Genmab.