The Janssen Pharmaceutical Companies of Johnson & Johnson announced the first presentation of Phase 2 data and updated Phase 1 data from the MajesTEC-1 study of teclistamab, an off-the-shelf T-cell investigational redirecting bispecific antibody, being studied for the treatment of patients with relapsed or refractory multiple myeloma.
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ATLANTA, Dec. 13, 2021 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced the first presentation of Phase 2 data and updated Phase 1 data from the MajesTEC-1 study of teclistamab, an off-the-shelf T-cell investigational redirecting bispecific antibody, being studied for the treatment of patients with relapsed or refractory multiple myeloma. With a median follow-up of nearly eight months, an overall response rate (ORR) of 62 percent was observed at the recommended subcutaneous (SC) Phase 2 dose (RP2D) of 1.5 mg/kg in heavily pretreated patients (n=150) across the Phase 1 and 2 studies who had received at least three prior lines of therapy and were triple-class exposed.1 Results were presented during the American Society of Hematology (ASH) 2021 Annual Meeting as an oral presentation (Abstract # 896) and selected as part of the Highlights of ASH program.1
MajesTEC-1 Data Highlights Fifty-eight percent of patients receiving teclistamab achieved a very good partial response (VGPR) or better; 29 percent achieved a complete response (CR) or better; and 21 percent achieved a stringent complete response (sCR).1 By intent to treat, 25 percent of patients (37/150) achieved MRD negativity at a threshold of 10-5 (95 percent CI, range, 18.0–32.4).1 In patients who achieved CR or better, the MRD negativity rate was 42 percent.1 The progression-free survival (PFS) rate at 9 months was 59 percent (95 percent CI, range, 48.8–67.0). Median overall survival (OS) was not reached.1 "Despite newly approved therapies for triple-class exposed patients with relapsed or refractory multiple myeloma, there remains a high unmet medical need," said Philippe Moreau, M.D.†, Clinical Hematology, University Hospital Hôtel-Dieu, Nantes, France and study investigator. "The objective responsive rate observed in this study suggests a potential benefit for many patients with triple-class exposed disease with an off-the-shelf therapy." As of September 2021, 165 patients were treated with teclistamab at the SC 1.5 mg/kg dose across both Phase 1 and Phase 2 of MajesTEC-1.1 The primary objectives of the MajesTEC-1 Phase 1 study (NCT03145181) were to identify the recommended SC RP2D (part 1) and characterize the safety and tolerability of teclistamab at the RP2D (part 2). The primary objective of the MajesTEC-1 Phase 2 study (NCT04557098) was to evaluate the efficacy of teclistamab at the RP2D, established at SC 1.5 mg/kg QW, as measured by ORR. Teclistamab had a tolerable safety profile, and no patients required a dose reduction.1 The most common nonhematologic adverse events (AEs) were cytokine release syndrome (72 percent; all grade 1/2 except for 1 grade 3 event that fully resolved; all resolved with no treatment discontinuation), injection site erythema (26 percent; all grade 1/2) and fatigue (25 percent; 2 percent grade 3/4).1 The most common hematologic AEs were neutropenia (66 percent; 57 percent grade 3/4), anemia (50 percent; 35 percent grade 3/4) and thrombocytopenia (38 percent; 21 percent grade 3/4).1 Five patients (3 percent; all grade 1/2) developed immune effector cell-associated neurotoxicity syndrome (ICANS) all resolved without discontinuation.1 "These longer-term data suggest that heavily pretreated patients in need of a new option may achieve sustained durable responses and high overall response rates for teclistamab," said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Hematologic Malignancies Disease Area Leader, Janssen Research & Development, LLC. "We remain focused on identifying new treatments for patients with relapsed or refractory multiple myeloma, including T-cell redirecting bispecific antibodies like teclistamab, for use alone and in novel immunotherapy regimens." TRIMM-2 Data Highlights About Teclistamab Teclistamab is currently being evaluated in several monotherapy (NCT04557098) and combination (NCT04586426, NCT04108195, NCT04722146, NCT05083169) studies. In 2020, the European Commission and the U.S. Food and Drug Administration (FDA) each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation from the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the U.S. FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimize drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need. The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.9 About DARZALEX FASPRO® DARZALEX FASPRO® is indicated for the treatment of adult patients with multiple myeloma:
DARZALEX FASPRO® in combination with bortezomib, cyclophosphamide, and dexamethasone is indicated for the treatment of adult patients with newly diagnosed AL amyloidosis. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Limitations of Use Full prescribing information for DARZALEX FASPRO® is available here. About Multiple Myeloma DARZALEX FASPRO® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hypersensitivity and Other Administration Reactions Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. Systemic Reactions In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients. Severe reactions included hypoxia, dyspnea, hypertension and tachycardia. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritis, chills, vomiting, nausea, and hypotension. Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions. Local Reactions In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management. Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis Neutropenia Thrombocytopenia Embryo-Fetal Toxicity The combination of DARZALEX FASPRO® with lenalidomide is contraindicated in pregnant women, because lenalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy. Interference with Serological Testing Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®. Interference with Determination of Complete Response ADVERSE REACTIONS The most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, pyrexia, cough, muscle spasms, back pain, vomiting, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema. The most common adverse reactions (≥20%) in patients with light chain (AL) amyloidosis who received DARZALEX FASPRO® are upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea, and cough. The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. Please see full Prescribing Information for DARZALEX FASPRO®. About the Janssen Pharmaceutical Companies of Johnson & Johnson Learn more at www.janssen.com. Follow us at @JanssenUS and @JanssenGlobal. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. †Dr. Moreau has served as a paid consultant to Janssen; he has not been paid for any media work. Kyprolis is a registered trademark of Amgen Inc. 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 and the potential benefits and treatment impact of teclistamab and DARZALEX FASPRO®. 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 Research & Development, LLC, Janssen Biotech, Inc., or any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions 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, 2021, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in the company's most recently filed Quarterly Report on Form 10-Q, 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 nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. Media Contact: Investor Relations: U.S. Medical Inquiries: 1 Moreau P et al. Updated Results From MajesTEC-1: Phase 1/2 Study of Teclistamab, a B-Cell Maturation Antigen x CD3 Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma. 2021 American Society of Hematology Annual Meeting. December 2021.
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