Phase 1b/Phase 2 studies planned in multiple myeloma and solid tumors

{{image}}Horsham, PA (Press Release) – Janssen Biotech, Inc. today announced that the com­pany has entered a clin­i­cal trial col­lab­o­ration with Bristol-Myers Squibb Company (BMS) to eval­u­ate the com­bi­na­tion of the first CD38-directed cytolytic anti­body dara­tu­mu­mab (DARZALEX®) and checkpoint inhibitor nivolumab (OPDIVO®) in Phase 1b /Phase 2 clin­i­cal studies in multiple myeloma and several solid tumor types. Nivolumab is devel­oped and com­mer­cial­ized by BMS. Janssen licensed dara­tu­mu­mab from Genmab A/S and is responsible for all global devel­op­ment, mar­ket­ing and manu­fac­tur­ing.

The multiple myeloma study will eval­u­ate the safety and tolerability of dara­tu­mu­mab in com­bi­na­tion with nivolumab with or without poma­lido­mide and dexa­metha­sone in re­lapsed/refractory multiple myeloma. The solid tumor studies will eval­u­ate the safety, tolerability and clin­i­cal benefit of dara­tu­mu­mab com­bined with nivolumab in patients with ad­vanced or metastatic tumors, in­­clud­ing non-small cell lung, head and neck, pancreatic, colorectal and triple neg­a­tive breast cancers. Additional tumor types may also be eval­u­ated. Studies are ex­pec­ted to start this year.

"Immunotherapy has vastly changed the way cancer is treated. We are excited to study this novel com­bi­na­tion of two poten­tially synergistic immuno­therapies," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development, LLC. "This agree­ment allows us to extend our footprint in immuno-oncology and will be a sig­nif­i­cant addi­tion to the growing body of clin­i­cal data for dara­tu­mu­mab in com­bi­na­tion with other novel agents, in a variety of tumor types."

DARZALEX is the first CD38-directed cytolytic anti­body approved any­where in the world. It was first approved by the U.S. Food and Drug Admin­istra­tion (FDA) in November 2015 as a mono­therapy for patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent or who are double refractory to a PI and immuno­modu­la­tory agent.¹ It is also approved in Europe, Canada and several other countries for a similar patient pop­u­la­tion.

DARZALEX was more recently approved by the FDA in November 2016 for use in com­bi­na­tion with lena­lido­mide (an immuno­modu­la­tory agent) and dexa­metha­sone, or bor­tez­o­mib (a PI) and dexa­metha­sone, in patients with multiple myeloma who have received at least one prior ther­apy.² DARZALEX received Break­through Therapy Desig­na­tion from the FDA for this indi­ca­tion in July 2016.³

About DARZALEX® (dara­tu­mu­mab) Injection, for Intravenous Infusion

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous use is the first CD38-directed cytolytic anti­body approved any­where in the world.¹ CD38 is a surface protein that is highly ex­pressed across multiple myeloma cells, re­gard­less of disease stage.⁴ dara­tu­mu­mab is believed to induce tumor cell death through multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­tox­icity (CDC), anti­body-dependent cellular cyto­tox­icity (ADCC) and anti­body-dependent cellular phago­cytosis (ADCP), as well as through apop­tosis, in which a series of molecular steps in a cell lead to its death.5 A subset of myeloid derived sup­pressor cells (MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by dara­tu­mu­mab.⁵ DARZALEX is being eval­u­ated in a com­pre­hen­sive clin­i­cal devel­op­ment pro­gram that in­cludes five Phase 3 studies across a range of treat­ment settings in multiple myeloma, such as in frontline and re­lapsed settings.^6,7,8,9,10 Additional studies are ongoing or planned to assess its poten­tial for a solid tumor indi­ca­tion and in other malignant and pre-malignant diseases in which CD38 is ex­pressed, such as smol­der­ing myeloma and non-Hodgkin's lym­phoma.^11,12,13 DARZALEX was the first cytolytic anti­body to receive regu­la­tory approval to treat re­lapsed or refractory multiple myeloma.¹

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a world­wide agree­ment, which granted Janssen an exclusive license to develop, manu­fac­ture and com­mer­cial­ize DARZALEX.14 DARZALEX is com­mer­cial­ized in the U.S. by Janssen Biotech, Inc. For more in­­for­ma­tion, visit www.DARZALEX.com.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^15,16 Refractory cancer occurs when a patient's disease is resistant to treat­ment or in the case of multiple myeloma, patients progress within 60 days of their last ther­apy.^17,18 Relapsed cancer means the disease has returned after a period of initial partial or com­plete remission.¹⁹ Globally, it is esti­mated that 124,225 people were diag­nosed, and 87,084 died from the disease in 2015.^20,21 While some patients with multiple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone fracture or pain, low red blood counts, fatigue, cal­cium elevation, kidney problems or in­fec­tions.²² Patients who relapse after treat­ment with standard ther­a­pies (including PIs or immuno­modu­la­tory agents) typically have poor prognoses and few remaining options.¹⁶

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS – None

WARNINGS AND PRECAUTIONS

Infusion Reactions – DARZALEX can cause severe in­fusion reac­tions. Approximately half of all patients ex­peri­enced a reac­tion, most during the first in­fusion. Infusion reac­tions can also occur with sub­se­quent in­fusions. Nearly all reac­tions occurred during in­fusion or within 4 hours of com­plet­ing an in­fusion. Prior to the in­tro­duc­tion of post-infusion medication in clin­i­cal trials, in­fusion reac­tions occurred up to 48 hours after in­fusion. Severe reac­tions have occurred, in­­clud­ing bron­cho­spasm, hypoxia, dyspnea, hyper­tension, laryngeal edema and pul­mo­nary edema. Signs and symp­toms may in­clude res­pira­tory symp­toms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symp­toms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypo­­tension.

Pre-medicate patients with antihistamines, anti­pyretics, and corticosteroids. Frequently monitor patients during the entire in­fusion. Interrupt in­fusion for reac­tions of any severity and institute medical man­agement as needed. Permanently dis­con­tinue ther­apy for life-threatening (Grade 4) reac­tions. For patients with Grade 1, 2, or 3 reac­tions, reduce the in­fusion rate when re-starting the in­fusion.

To reduce the risk of delayed in­fusion reac­tions, admin­ister oral corticosteroids to all patients fol­low­ing DARZALEX in­fusions. Patients with a history of chronic obstructive pul­mo­nary disease may require addi­tional post-infusion medications to man­age res­pira­tory com­pli­ca­tions. Consider pre­scrib­ing short- and long-acting bron­cho­di­lators and inhaled corticosteroids for patients with chronic obstructive pul­mo­nary disease.

Interference with Serological Testing - dara­tu­mu­mab binds to CD38 on red blood cells (RBCs) and results in a pos­i­tive Indirect Antiglobulin Test (Indirect Coombs test). Dara­tu­mu­mab-mediated pos­i­tive indirect antiglobulin test may persist for up to 6 months after the last dara­tu­mu­mab in­fusion. Dara­tu­mu­mab bound to RBCs masks detection of anti­bodies to minor an­ti­gens in the patient's serum. The deter­mi­na­tion of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this inter­fer­ence with serol­o­gical testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.

Neutropenia - DARZALEX may in­­crease neu­tro­penia induced by back­ground ther­apy. Monitor com­plete blood cell counts periodically during treat­ment according to manu­­fac­­turer's pre­scrib­ing in­­for­ma­tion for back­ground ther­a­pies. Monitor patients with neu­tro­penia for signs of in­fec­tion. DARZALEX dose delay may be required to allow re­cov­ery of neu­tro­phils. No dose reduction of DARZALEX is rec­om­mended. Consider sup­port­ive care with growth factors.

Thrombocytopenia - DARZALEX may in­­crease thrombo­cytopenia induced by back­ground ther­apy. Monitor com­plete blood cell counts periodically during treat­ment according to manu­­fac­­turer's pre­scrib­ing in­­for­ma­tion for back­ground ther­a­pies. DARZALEX dose delay may be required to allow re­cov­ery of platelets. No dose reduction of DARZALEX is rec­om­mended. Consider sup­port­ive care with transfusions.

Interference with Determination of Complete Response - dara­tu­mu­mab is a human IgG kappa mono­clonal anti­body that can be detected on both, the serum protein electrophoresis (SPE) and immuno­fix­a­tion (IFE) assays used for the clin­i­cal monitoring of endogenous M-protein. This inter­fer­ence can impact the deter­mi­na­tion of com­plete response and of disease pro­gres­sion in some patients with IgG kappa myeloma protein.

Adverse Reactions – In patients who received DARZALEX in com­bi­na­tion with lena­lido­mide and dexa­metha­sone, the most frequently reported adverse reac­tions (incidence ≥20%) were: neu­tro­penia (92%), thrombo­cytopenia (73%), upper res­pira­tory tract in­fec­tion (65%), in­fusion reac­tions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%) and pyrexia (20%). The over­all in­ci­dence of serious adverse reac­tions was 49%. Serious adverse reac­tions were pneu­monia (12%), upper res­pira­tory tract in­fec­tion (7%), influenza (3%) and pyrexia (3%).

In patients who received DARZALEX in com­bi­na­tion with bor­tez­o­mib and dexa­metha­sone, the most frequently reported adverse reac­tions (incidence ≥20%) were: thrombo­cytopenia (90%), neu­tro­penia (58%), periph­eral sensory neu­rop­athy (47%), in­fusion reac­tions (45%), upper res­pira­tory tract in­fec­tion (44%), diarrhea (32%), cough (27%), periph­eral edema (22%), and dyspnea (21%). The over­all in­ci­dence of serious adverse reac­tions was 42%. Serious adverse reac­tions were upper res­pira­tory tract in­fec­tion (5%), diarrhea (2%) and atrial fibrillation (2%).

In patients who received DARZALEX as mono­therapy, the most frequently reported adverse reac­tions (incidence ≥20%) were: neu­tro­penia (60%), thrombo­cytopenia (48%), in­fusion reac­tions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper res­pira­tory tract in­fec­tion (20%). Serious adverse reac­tions were reported in 51 (33%) patients. The most frequent serious adverse reac­tions were pneu­monia (6%), general physical health deterioration (3%), and pyrexia (3%).

DRUG INTERACTIONS

Effect of Other Drugs on dara­tu­mu­mab: The coadministration of lena­lido­mide or bor­tez­o­mib with DARZALEX did not affect the phar­ma­co­ki­netics of dara­tu­mu­mab.

Effect of dara­tu­mu­mab on Other Drugs: The coadministration of DARZALEX with bor­tez­o­mib did not affect the phar­ma­co­ki­netics of bor­tez­o­mib.

About the Janssen Pharma­ceu­tical Com­panies

At the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson, we are work­ing to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease in­spires us. We bring together the best minds and pursue the most promising science. We are Janssen. We col­lab­o­rate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal.

Cautions Concerning Forward-Looking Statements

This press release con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing planned clin­i­cal trials and ex­pec­ted expansion of clin­i­cal data on dara­tu­mu­mab. 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 Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and un­cer­tain­ties in­clude, but are not limited to: chal­lenges in­her­ent in prod­uct research and devel­op­ment, in­­clud­ing the uncertainty of clin­i­cal success and obtaining regu­la­tory approvals; uncertainty of commercial success for new prod­ucts or new indi­ca­tions; 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 January 3, 2016, 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

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13. Janssen Research & Development, LLC. An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 Nov 11]. https://clinicaltrials.gov/ct2/show/NCT02413489?term=lym2001&rank=1 Identifier: NCT02413489.
14. Janssen Biotech, Inc. "Janssen Biotech Announces Global License and Development Agreement ^[5]." Issued August 30, 2012
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Source: Janssen Biotech, Inc.