JANSSEN-PHARMA-J&J

The Janssen Pharmaceutical Companies of Johnson & Johnson announced today updated results from an ongoing Phase 1 first-in-human dose escalation study (NCT03145181 ) of teclistamab (JNJ-64007957) for the treatment of relapsed or refractory multiple myeloma (MM). In heavily pretreated patients, the overall response rate (ORR) with teclistamab was 73 percent (16/22) at the recommended SC Phase 2 dose (RP2D).¹ These results for the SC formulation support the recommended dose for the pivotal Phase 2 registration trial, which has started. In addition, updated results for the intravenous (IV) formulation demonstrate the durability of responses.¹

“The data presented today for the subcutaneous formulation build on promising results presented earlier this year for the intravenous regimen,” said Alfred Garfall, M.D.,* Assistant Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, and presenting author. “The preliminary efficacy, including durability of responses, combined with the initial safety profile in this highly pretreated population is encouraging and supports further studies of teclistamab in patients with relapsed or refractory multiple myeloma who are in need of additional treatment options.”

The study is conducted in two parts: dose escalation (part 1) and dose expansion (part 2), and enrolled patients with MM who had relapsed or were refractory to established therapies and had previously been treated with a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).¹ Patients had received a median of six prior lines of treatment (range, 2-14); 96 percent were triple-class exposed, 81 percent were triple-class refractory, 91 percent were refractory to the last line of therapy, and 39 percent were penta-drug refractory (to two or more immunomodulatory agents, two or more PIs, and an anti-CD38 therapy).¹ Prognosis is poor for patients with refractory MM as treatment options are limited.¹

The RP2D was identified as 1500 µg/kg SC, and the maximum tolerated dose has not been identified. Fifty-five percent of patients achieved a very good partial response or better (12/22), and 23 percent of patients (5/22) achieved a complete response (CR) or better with RP2D SC dosing.¹ After median follow-up of 3.9 months (range of 1.7–7.4 months), 94 percent (15/16) of responders treated with the SC RP2D were alive and progression-free.¹ Responses appeared durable and deepened over time at the RP2D.¹

Of the 11 patients who achieved CR and were evaluable for minimal residual disease (MRD) analysis across all IV and SC doses, eight patients attained MRD-negative CR at a threshold of 10^-6 and one at a 10^-5 threshold. Sustained MRD-negativity was confirmed for all five evaluable patients across the IV and SC cohorts.¹

At the SC RP2D, 64 percent of patients experienced cytokine release syndrome (CRS) events, all of which were Grade 1 or 2 and generally confined to step-up, or a gradual increase in dosing, and first full doses.¹ No patients discontinued treatment due to CRS. Of 33 treated patients at the RP2D, only one neurotoxicity event, which was reversible, was observed.¹ Selection of the 1500ug/kg SC RP2D is supported by promising safety, efficacy, pharmacokinetics and pharmacodynamics. The SC formulation may provide an opportunity for less frequent dosing for patients than the IV formulation, although this has not been explored in the current study.¹

The most common adverse events (AEs) (all grade ≥20 percent) for the RP2D in the SC cohort were CRS (64 percent); neutropenia (52 percent); anaemia (39 percent); thrombocytopenia (33 percent); leukopenia (33 percent); and fatigue (24 percent).¹ In patients who experienced Grade 3 and above AEs (≥20 percent), the most common at the RP2D SC dose were neutropenia (33 percent); and anaemia (21 percent).¹ One Grade 5 treatment related AE (pneumonia) was reported at the 80 µg/kg IV dose, but none at the RP2D.¹

 “We are committed to exploring treatment options that use promising modalities in multiple myeloma, including bispecific antibodies like teclistamab, that increase treatment responses through antigen targeting,” said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Global Head, Hematologic Malignancies, Janssen Research & Development, LLC. “Our research in multiple myeloma is broad, exploring multiple targets through a variety of approaches. We continue to identify new treatment options, particularly for patients who have relapsed or become refractory to existing therapies.”

 “These initial results demonstrate the early promise of bispecific antibodies for people living with multiple myeloma and may, in the future, provide healthcare professionals with another tool in their arsenal to treat this devastating disease.” said Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. “Their development builds on our rich heritage in multiple myeloma, where we have continually sought to investigate new treatment strategies that have the potential to address remaining unmet needs.”

Additional pharmacokinetic and ex vivo data for teclistamab will be highlighted in a poster on Monday, December 7 from 4:00pm to 12:30am CET (Abstract #3194).² This study evaluated the ability of teclistamab to induce cytotoxicity and T-cell activation.²

 *Alfred Garfall is lead investigator of the NCT03145181 study and was not compensated for any media work

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About Teclistamab
Teclistamab is an investigational bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3. BCMA is expressed at high levels on multiple myeloma cells.^3,4,5,6,7 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce cytotoxicity of the targeted cells.^5,6 Results from preclinical studies demonstrate that teclistamab kills myeloma cell lines and bone marrow-derived myeloma cells from heavily pretreated patients.⁶

Teclistamab is currently being evaluated in a Phase 2 clinical study for the treatment of relapsed or refractory multiple myeloma (NCT04557098 ) and is also being explored in combination studies (NCT04586426 , NCT04108195 ). The production and development of the antibody followed Janssen Biotech, Inc.'s licensing agreement with Genmab for use of its DuoBody^®  technology platform.^** In October and November 2020, the European Commission and the U.S. Food and Drug Administration (FDA), respectively, granted teclistamab orphan designation for the treatment of multiple myeloma.^8,9

^** DuoBody is a registered trademark of Genmab A/S.

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.¹⁰ In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.¹¹ Around 50 percent of newly diagnosed patients do not reach five-year survival,^12,13 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.¹⁴

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.¹⁵ Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course.¹⁶ While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.¹⁷ Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.¹⁸

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com . Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen Research & Development, LLC, Janssen Biotech, Inc., and Janssen-Cilag Ltd., Middle East are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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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. 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 Pharmaceutica NV and/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 December 29, 2019, 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. Neither 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.

References  

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¹ Garfall, AL et al. Updated Phase 1 Results of Teclistamab, a B-cell Maturation Antigen (BCMA) × CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM). 2020 American Society of Hematology Annual Meeting . December 2020.
² Girgis, S et al. Translational Approach of Using Ex Vivo Cytotoxicity and Early Clinical Data to Predict Teclistamab Efficacious Therapeutic Range in Multiple Myeloma Patients. 2020 American Society of Hematology Annual Meeting . December 2020.
³ Labrijn AF, Meesters JI, de Goeij BECG, et al. Efficient Generation of Stable Bispecific IgG1 by Controlled Fab-arm Exchange. Proc Natl Acad Sci USA . 2013;110(13):5145-5150.
⁴ Frerichs KA, Broekmans MEC, Marin Soto JA, et al. Preclinical Activity of JNJ-7957, a Novel BCMAxCD3 Bispecific Antibody for the Treatment of Lumtiple Myeloma, is Potentiated by Daratumumab. Clin Cancer Res . 2020; doi: 10.1158/1078-0432.CCR-19-2299.
⁵ Cancer Research Institute. Adoptive Cell Therapy: TIL, TCR, CAR T, AND NK CELL THERAPIES. Available at: https://www.cancerresearch.org/immunotherapy/treatment-types/adoptive-cell-therapy Last accessed: December 2020.
⁶ Cho SF, Anderson KC and Tai YT. Targeting B cell maturation antigen (BCMA) in Multiple Myeloma; Potential Uses of BCMA-Based Immunotherapy. Frontiers in Immunology . 2018; 9: 1821.
⁷ Benonisson H, Altintas I, Sluijter M et al. CD3-Bispecific Antibody Therapy Turns Solid Tumors into Inflammatory Sites but Does Not Install Protective Memory. Molecular Cancer Therapeutics . 2019 (18) (2) 312-322.
⁸ European Medicines Agency. September 2020 Committee for Orphan Medicinal Products (COMP) meeting report on the review of applications for orphan designation. Available at: https://www.ema.europa.eu/en/documents/committee-report/comp-meeting-report-review-applications-orphan-designation-september-2020_en.pdf Last accessed: December 2020.
⁹ U.S. Food and Drug Administration. Search Orphan Drug Designations and Approvals – Teclistamab. Available at: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=782920 Last accessed: December 2020.
¹⁰ American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction Last accessed: December 2020.
¹¹ GLOBOCAN 2018. Cancer Today Population Factsheets: Europe Region. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf Last accessed: December 2020.
¹² American Society of Clinical Oncology. Multiple Myeloma: Statistics. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/statistics Last accessed: December 2020.
¹³ Cancer Research UK. Myeloma statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma Last accessed: December 2020.
¹⁴ Costa LJ, Gonsalves WI and Kumar SK. Early mortality in multiple myeloma. Leukemia. 2015;29:16168.
¹⁵ Abdi J, Chen G, Chang H, et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget . 2013;4:2186–207.
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CP-195987
December 2020

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