RARITAN, NJ, December 5, 2020 / PRNewswire / – Janssen Pharmaceuticals Companies of Johnson & Johnson today announced initial data from the first Phase 1 human dose-escalation study of talquetamab (JNJ-64407564) for the treatment of myeloma multiple relapsing or refractory (NCT03399799). Talquetamab is a first-order bispecific antibody and the only one under study that targets both GPRC5D, a new target in multiple myeloma, and CD3 on T cells. The first results for the subcutaneous (SC) formulations ) and intravenous (IV) show encouraging clinical activity against the GPRC5D target, which is highly expressed on multiple myeloma cells and associated with poor prognostic factors.1,2,3 At the SC recommended phase 2 dose (RP2D), the overall response rate (ORR) was 69 percent (9/13) and 39 percent achieved a very good partial response (VGPR) or better. The data will be presented at the American Society of Hematology (ASH) Annual Meeting 2020 as an oral presentation on Saturday 5 December at 5:00 p.m. ET (Abstract # 290).
“There is an urgent need for continued innovation in treatments for multiple myeloma – particularly for patients who have relapsed on other therapies – and the results presented today for talquetamab are encouraging,” said Ajai Chari, MD, Professor of Medicine, Director of Clinical Research in the Multiple Myeloma Program and Associate Director of Clinical Research, Mount Sinai Cancer Clinical Trials Office. “The overall phase 1 response rate and safety profile support further study of talquetamab as monotherapy and in combination for patients with few treatment options.
Investigators identified the RP2D of 405 µg / kg SC and concluded that subcutaneous treatment may offer an opportunity for less frequent dosing than the intravenous formulation. A response was observed in 6/9 triple-class refractory patients and 2/2 patients refractory to penta-drugs. Pharmacokinetic results indicate target exposure levels for RP2D. At RP2D of 405 µg / kg SC, pharmacodynamic data demonstrate constant T cell activation, cytokine production and redistribution.
Patients received talquetamab at doses of 1 to 180 µg / kg for IV administration and 5 to 800 µg / kg for the SC formulation. Results from the phase 1 study showed responses in patients treated with talquetamab in all dose groups; The median time to first confirmed response for all doses was one month (range 0.2 to 3).4
The phase 1 study enrolled patients (n = 157) with multiple myeloma who had progressed or could not tolerate any of the existing therapies available. Patients had received a median of six prior lines of treatment (range, 2-20); 87% were refractory to the last line of treatment, 82% were refractory to three classes and 33% were refractory to penta-drugs with two or more immunomodulatory agents, two or more PIs and anti-CD38 therapy. The study is carried out in two parts: increasing the dose (part 1) and increasing the dose (part 2).4
In the Phase 1 study, the adverse events (AEs) to RP2D that occurred with a grade 3 frequency ≥ 25% in the SC cohort were neutropenia (42%). With SC administration, cytokine release syndrome (CRS) was observed in 64 percent of patients and was low-grade with no CRS event of grade 3 or greater than RP2D. CRS occurred at a median of two days after administration, and the median duration of CRS was also two days. The incidence of neurotoxicity was five percent at RP2D, with no patient presenting grade 3 or greater events with SC administration.4
“GPRC5D is a new target in the treatment of multiple myeloma and, as a bispecific antibody that engages T cells by also targeting CD3, talquetamab is emerging as a potential treatment option for heavily pretreated patients,” said declared Yusri Elsayed, MD, MHSc., Ph.D., Vice President, Global Head, Hematologic Malignancies, Janssen Research & Development, LLC. “Based on the preliminary efficacy, safety, pharmacokinetics and pharmacodynamics data presented today, we are committed to fully exploring the promise of talquetamab in multiple myeloma.”
Talquetamab is a first-order experimental bispecific antibody targeting both GPRC5D, a novel target in multiple myeloma, and CD3, the T-cell receptor.4 CD3 is involved in the activation of T lymphocytes and GPRC5D is highly expressed on multiple myeloma cells.4.5,6 Results from preclinical studies in mouse models demonstrate that talquetamab induces T-cell-mediated destruction of multiple myeloma cells expressing GPRC5D through recruitment and activation of CD3-positive T cells and inhibits tumor formation and growth .6
Talquetamab is currently being evaluated in a phase 1/2 clinical study for the treatment of relapsed or refractory multiple myeloma and is also being studied in combination studies. Development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for the use of its DuoBody® technological platform. *
* DuoBody® is a registered trademark of Genmab A / S.
About multiple myeloma
Multiple myeloma is an incurable cancer of the blood that affects a type of white blood cell called plasma cells, which are found in the bone marrow.7.8 When damaged, these plasma cells spread quickly and replace normal cells with tumors in the bone marrow. In 2020, it is estimated that more than 32,000 people will be diagnosed and nearly 13,000 will die from the disease in the United States.9 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell count, fatigue, high calcium levels. , kidney problems or infections.ten
About Johnson & Johnson Janssen Pharmaceutical Companies
At Janssen, we are creating a future where illness is a thing of the past. We are the pharmaceutical companies of Johnson & Johnson, working tirelessly to make this future a reality for patients around the world by fighting disease with science, improving access with ingenuity, and healing despair with the heart. We focus on those areas of medicine where we can make the biggest difference: cardiovascular and metabolism, immunology, infectious diseases and vaccines, neuroscience, oncology and pulmonary hypertension.
Find out more at www.janssen.com. Follow us on www.twitter.com/JanssenGlobal and www.twitter.com/JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Cautions Regarding 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 impact of talquetamab treatment. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If the underlying assumptions prove to be incorrect or known or unknown risks or uncertainties materialize, actual results could differ materially from the expectations and projections of Janssen Research & Development, LLC. or any of the other Janssen and / or Johnson & Johnson pharmaceutical companies. Risks and uncertainties include, but are not limited to: the challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; the uncertainty of business success; manufacturing difficulties and delays; competition, including technological advances, new products and patents obtained by competitors; patent challenges; efficacy or safety issues of the product leading to product recalls or regulatory action; changes in the behavior and spending habits of buyers of health products and services; changes in applicable laws and regulations, including global health care reforms; and trends towards containing health care costs. 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 year ended. December 29, 2019, including in the sections entitled “Caution Regarding Forward-Looking Statements” and “Point 1A. Risk Factors ”, and in the company’s latest Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these documents are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceuticals nor Johnson & Johnson undertakes to update any forward-looking statements as a result of new information or future events or developments.
1 Black-smith Sci Transl Med 11 (485): eaau7746.
2 Pillarisetti Some blood 135 (15): 1232.
3 Atamaniuk Eur J Clin Invest 42 (9): 953. CD3, differentiation cluster 3; MGUS, monoclonal gammopathy of undetermined importance; SMM, burning multiple myeloma.
4 Chari A et al. A Phase 1, First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x CD3 Bispecific Antibody, in patients with relapse and / or refractory multiple myeloma (RRMM): https: / /www.ncbi.nlm.nih.gov/pmc/articles/PMC7408718/. Accessed November 2020
5 Labrijn AF et al. Proc Natl Acad Sci United States. 2013; 110: 5145.
6 Cohen, Y. et al. Hematology. 2013 Nov; 18 (6): 348-51.
seven Kumar SK et al. Leukemia. 2012 Jan; 26 (1): 149-57.
8 American Cancer Society. “What is multiple myeloma?”. Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed November 2020.
9 American Cancer Society: Cancer Facts and Statistics. American Cancer Society | Cancer facts and statistics. https://cancerstatisticscenter.cancer.org/#!/cancer-site/Myeloma. Accessed November 2020.
tenAmerican Cancer Society. “Key Statistics on Multiple Myeloma”. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed January 2020.
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