Results featured at the 57th Annual American Society of Hematology Meeting and Exposition:

• 72 per­cent of re­lapsed or refractory multiple myeloma patients treated with dara­tu­mu­mab com­bi­na­tion ther­apy did not progress or relapse after 18 months of treat­ment (GEN 503)
• Daratumumab in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone produced rapid, deep and durable responses in re­lapsed and refractory multiple myeloma patients who had received at least two (median of 3.5) prior lines of ther­apy, in­­clud­ing two or more consecutive cycles of lena­lido­mide and bor­tez­o­mib, and were refractory to their last line of treat­ment (MMY1001 Phase1b)
• Single-agent dara­tu­mu­mab dem­onstrated a median over­all survival of 20 months in heavily pre-treated re­lapsed and refractory multiple myeloma patients who have exhausted other approved treat­ment options. A partial response or better was achieved by 31 per­cent of patients, and 83 per­cent achieved stable disease or better (GEN 501 & MMY2002)

Beerse, Belgium (Press Release) – Janssen-Cilag Inter­na­tional NV announced new data from the ongoing Phase 1/2 GEN503 inves­ti­ga­tional study showing the human CD38-directed mono­clonal anti­body dara­tumumab, in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, yielded an over­all response rate (ORR) of 81 per­cent in re­lapsed or refractory multiple myeloma patients who had received a median of two prior ther­a­pies. After 18 months of treat­ment, investigators observed an over­all survival (OS) rate of 90 per­cent, with 72 per­cent of patients experiencing pro­gres­sion-free survival (PFS).¹

The data, from the cohort expansion phase of GEN503, were presented today during the official press pro­gramme at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL, U.S. and will be presented in full during an oral abstract session on Monday, December 7 at 7:30 a.m. Eastern Time (ET) / 1:30 p.m. Central European Time (CET).

“Daratumumab has already shown pronounced activity as a single-agent immuno­therapy in a heavily pre-treated patient pop­u­la­tion with re­lapsed and refractory multiple myeloma. These findings suggest that it has the poten­tial to induce rapid, deep, and durable responses in com­bi­na­tion with standard treat­ment in earlier lines of ther­apy,” said lead study author, Pro­fessor Torben Plesner, Department of Hematology, Vejle Hospital, Vejle, Denmark. “These data are particularly exciting, as 72 per­cent of patients treated with dara­tu­mu­mab com­bi­na­tion ther­apy did not progress or relapse after 18 months of treat­ment.”

The cohort expansion phase of the open label, inter­na­tional, multicentre, dose escalating Phase 1/2 GEN503 study enrolled 32 patients who had received a median of two prior lines of ther­apy. Stringent com­plete response (sCR) was reported in 25 per­cent of patients (n=8), com­plete response (CR) was reported in 9 per­cent (n=3), very good partial response (VGPR) was reported in 28 per­cent (n=9), and partial response (PR) was reported in 19 per­cent (n=6). Among all patients, the median times to first and best response were one month (95 per­cent con­fi­dence in­ter­val [CI], 0.5-5.6) and 5.1 months (95 per­cent CI, 0.5-14.4), re­spec­tive­ly. The median duration of response was not reached.¹

“Daratumumab is cur­rently undergoing regu­la­tory review by the European Medicines Agency (EMA) as mono­therapy for re­lapsed and refractory multiple myeloma in heavily pre-treated patients. These new data indicate its poten­tial as a treat­ment option for re­lapsed or refractory multiple myeloma in com­bi­na­tion with standard treat­ments. Janssen strongly believes our robust clin­i­cal trial pro­gramme will allow us to unlock the full poten­tial of this first human CD38-directed mono­clonal anti­body, both as a single agent and in com­bi­na­tion with standard treat­ment,” said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. “It’s very exciting to see such compelling data as part of more than 40 com­pany-sponsored abstracts being presented at ASH this year.”

The two-part GEN503 study is com­prised of a dose escalation study (part 1) and a cohort expansion study (part 2). In part 1, patients received dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide (25 mg orally on days 1 through 21 of every 28-day cycle) and dexa­meth­a­sone (40 mg in­tra­venously and orally once weekly). Dara­tumumab 2-16 mg/kg body weight was admin­istered as an in­tra­venous in­fusion given weekly for the first eight weeks, then bi-weekly (every two weeks) for the next 16 weeks, and then monthly until disease pro­gres­sion or unmanageable toxicity for 24 months in total. In part 2, all patients were admin­istered the rec­om­mended Phase 2 dara­tu­mu­mab dose (16 mg/kg), patients refractory to lena­lido­mide were excluded, and patients with at least one prior line of ther­apy were in­cluded.²

In this study, the most common adverse events (AEs) in­cluded neu­tro­penia (84 per­cent), cough (47 per­cent), muscle spasms (44 per­cent) and diarrhoea (44 per­cent). Sixteen patients (50 per­cent) ex­peri­enced serious AEs, but only neu­tro­penia (n=3), gastroenteritis (n=2) and pyrexia (n=2) occurred in more than one patient. Eighteen patients (56 per­cent) had in­fusion reac­tions; these were generally mild to mod­er­ate (Grade ≤2) and usually occurred during the first in­fusion. Infusion reac­tions were man­aged with pre-medication or by slowing in­fusion rate. No addi­tional safety signals were observed.¹

Other Dara­tu­mu­mab Presentations at ASH

In a separate presentation researchers will present updated data from an ongoing open-label, multicentre, Phase 1b study showing dara­tu­mu­mab in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone produced rapid, deep and durable responses in re­lapsed or refractory multiple myeloma patients who had received at least two (median of 3.5) prior lines of ther­apy, in­­clud­ing two or more consecutive cycles of lena­lido­mide and bor­tez­o­mib, and were refractory to their last line of treat­ment. The com­bi­na­tion of dara­tu­mu­mab with poma­lido­mide and dexa­meth­a­sone was well-tolerated and resulted in little addi­tional toxicity with the exception of dara­tu­mu­mab-related in­fusion reac­tions. The data will be presented during an oral abstract session on Monday, December 7 at 7:45 a.m. ET / 1:45 p.m. CET.³

Researchers also presented data from a com­bined efficacy analysis of the open-label, multicentre Phase 1/2 GEN501 and Phase 2 MMY2002 (SIRIUS) trials, which in­cluded heavily pre-treated patients with re­lapsed and refractory multiple myeloma who have exhausted other approved treat­ment options and whose disease was progressive at enrolment. After a median follow-up of 14.8 months, investigators esti­mated the median OS for single-agent dara­tu­mu­mab (16 mg/kg) would be 19.9 months (95 per­cent CI, 15.1–not estimable) for the com­bined analysis if patients con­tinued treat­ment. A partial response or better was achieved by 31 per­cent of patients, and 83 per­cent achieved stable disease or better. These data were presented during an oral abstract session on Saturday, December 5.⁴

About Multiple Myeloma

Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is char­ac­ter­ised by an excessive proliferation of plasma cells.⁵ MM is the second most common form of blood cancer, with around 39,000 new cases world­wide in 2012.⁶ MM most commonly affects people over the age of 65 and is more common in men than in women.⁷ Across Europe, five-year survival rates are 23 per­cent to 47 per­cent of people diag­nosed.⁸ Almost 29 per­cent of patients with MM will die within one year of diag­nosis.⁹ Although treat­ment may result in remission, unfortunately patients will most likely relapse as there is cur­rently no cure. While some patients with MM have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone problems, low blood counts, cal­cium elevation, kidney problems or in­fec­tions.⁷ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing pro­te­a­some inhibitors (PIs) and immun­o­modu­la­tory agents (IMiDs), have poor prognoses and few treat­ment options avail­able.¹⁰

About Dara­tu­mu­mab

Daratumumab is a human CD38-directed mono­clonal anti­body which binds with high affinity to CD38, a surface protein that is over-expressed on most, if not all, multiple myeloma cells.¹¹ Dara­tumumab is believed to induce rapid tumour cell death through apop­tosis, in which a series of molecular steps in a cell lead to its death12,13 and multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­toxicity (CDC), anti­body-dependent cellular cyto­toxicity (ADCC) and anti­body-dependent cellular phago­cytosis (ADCP).^12,14,15 Five Phase 3 clin­i­cal studies with dara­tu­mu­mab in re­lapsed and frontline settings are cur­rently ongoing. Additional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant diseases in which CD38 is ex­pressed, such as smoul­der­ing myeloma and non-Hodgkin lym­phoma. For more in­­for­ma­tion, please see www.clinicaltrials.gov.

Daratumumab is cur­rently under accelerated assess­ment by the European Medicines Agency. In the U.S., dara­tu­mu­mab is approved by the Food and Drug Admin­istra­tion (FDA) 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. Continued approval for this indi­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firmatory trials.¹²

About Janssen

The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson are dedicated to addressing and solving the most im­por­tant unmet medical needs of our time, in­­clud­ing on­col­ogy (e.g. multiple myeloma and prostate cancer), immunology (e.g. psoriasis), neuroscience (e.g. schizophrenia, dementia and pain), infectious disease (e.g. HIV/AIDS, hepatitis C and tuberculosis), and cardiovascular and metabolic diseases (e.g. diabetes). Driven by our commitment to patients, we develop sustainable, integrated health­care solu­tions by work­ing side-by-side with health­care stakeholders, based on part­ner­ships of trust and transparency. More in­­for­ma­tion can be found on www.janssen-emea.com. Follow us on www.twitter.com/janssenEMEA for our latest news.

Janssen-Cilag Inter­na­tional NV is part of the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson.

Janssen in Oncology

Our goal is to fundamentally alter the way cancer is under­stood, diag­nosed and man­aged, reinforcing our commitment to the patients who in­spire us. In looking to find inno­va­tive ways to address the cancer chal­lenge, our pri­mary efforts focus on several treat­ment and prevention solu­tions. These in­clude a focus on haematologic malig­nan­cies, prostate cancer and lung cancer; cancer interception with the goal of devel­op­ing prod­ucts that interrupt the carcinogenic process; bio­­markers that may help guide targeted, individualised use of our ther­a­pies; as well as safe and effective identi­fi­ca­tion and treat­ment of early changes in the tumour microenvironment.

Cautions Concerning Forward-Looking Statements

This press release con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing prod­uct devel­op­ment. The reader is cautioned not to rely on these for­ward-looking state­ments. These state­ments are based on current ex­pec­ta­tions of future events. If under­lying assump­tions prove inaccurate or known or unknown risks or un­cer­tain­ties ma­teri­alize, actual results could vary ma­teri­ally from the ex­pec­ta­tions and projections of any of the Janssen Pharma­ceu­tical Com­panies or Johnson & Johnson. Risks and un­cer­tain­ties in­clude, but are not limited to: chal­lenges and un­cer­tain­ties in­her­ent in new prod­uct devel­op­ment, in­­clud­ing the uncertainty of clin­i­cal success and of obtaining regu­la­tory approvals; com­pe­ti­tion, in­­clud­ing technological ad­vances, new prod­ucts and patents attained by com­pet­i­tors; chal­lenges to patents; changes to appli­­cable laws and reg­u­la­tions, in­­clud­ing global health care reforms; and trends to­ward health care cost con­tainment. A further list and description of these risks, un­cer­tain­ties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2014, in­­clud­ing in Exhibit 99 thereto, and the com­pany's sub­se­quent filings with the Se­cu­ri­ties and Exchange Com­mis­sion. Copies of these filings are avail­able online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharma­ceu­tical Com­panies or Johnson & Johnson under­takes to update any for­ward-looking state­ment as a result of new in­­for­ma­tion or future events or devel­op­ments.

References

1. Plesner, T. Daratumumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma: Updated Results of a Phase 1/2 Study (GEN503). Presented at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition, December 6, 2015, Orlando, FL. Press Briefing.
2. ClinicalTrials.gov. Daratumumab in com­bi­na­tion with lenalidomide and dexamethasone in relapsed and relapsed-refractory multiple myeloma (NCT01615029). Available at https://www.clinicaltrials.gov/ct2/show/NCT01615029. Last Accessed November 2015.
3. Chari A, Lonial S, Suvannasankha A, et al. Open-label, multicenter, phase 1b study of daratumumab in com­bi­na­tion with poma­lido­mide and dexamethasone in patients with ≥2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma (MM) (Abstract #508). Presented at the 57th Annual American Society of Hematology Meeting and Exposition, December 7, 2015, Orlando, FL.
4. Usmani S, Weiss B, Bahlis NJ, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. (Abstract #29). Presented at the 57th Annual American Society of Hematology Meeting and Exposition, December 5, 2015, Orlando, FL.
5. American Society of Clinical Oncology. Multiple myeloma: overview. Available at: http://www.cancer.net/cancer-types/multiple-myeloma/overview Last accessed November 2015.
6. GLOBOCAN 2012. Multiple myeloma. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=62968&Textp=Europe&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=13&type=0&window=1&submit=%C2%A0Execute Last accessed November 2015.
7. American Cancer Society. Multiple myeloma: detailed guide. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf Last accessed November 2015.
8. Cancer Research UK. Myeloma survival statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/myeloma/survival/multiple-myeloma-survival-statistics Last accessed November 2015.
9. Costa LJ, Gonsalves WI, Kumar SK. Early mortality in multiple myeloma. Leukemia. 2015;29:1616-8.
10. Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26:149-57.
11. Fedele G, di Girolamo M, Recine U, et al. CD38 Ligation in peripheral blood mononuclear cells of myeloma patients induces release of protumorigenic IL-6 and impaired secretion of IFNγ cytokines and proliferation. Mediators Inflamm. 2013;2013:564687.
12. DARZALEX Prescribing Information, November 2015. Available at https://www.darzalex.com/shared/product/darzalex/darzalex-prescribing-information.pdf Last accessed November 2015.
13. Jansen JH, Bross P, Overdijk MB, et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012;120(21):abstract 2974.
14. de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840-8.
15. 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(2):311-21.

Source: Janssen.