Janssen Presents Longer-Term Data for TECVAYLI® (teclistamab-cqyv) Showing a Duration of Response of 22 Months in Patients with Relapsed or Refractory Multiple Myeloma

The Janssen Pharmaceutical Companies of Johnson & Johnson announced today long-term data from the pivotal Phase 1/2 MajesTEC-1 study showing the sustained efficacy and safety of TECVAYLI^® (teclistamab-cqyv) in the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who are triple-class exposed and previously received treatment with three or more prior lines of therapy. These results showed that nearly half of patients achieved a complete response (CR) or better which underscore the continued durable responses seen in this patient population.¹ These data were featured at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #8011) along with additional poster presentations from MajesTEC-1 featuring data on the durability of responses with TECVAYLI^® biweekly dosing as well as an evaluation of the use of tocilizumab, given prophylactically, to examine potential reduction of cytokine release syndrome (CRS) in the management of RRMM patients treated with TECVAYLI^®.

Extended follow-up data from the pivotal Phase 1/2 MajesTEC-1 study of TECVAYLI^® demonstrate an overall response rate (ORR) of 63 percent, with responses that continued to deepen over time.¹ More than 45 percent of patients have now achieved a CR or better, and median time to CR or better was 4.6 months (range, 1.6-18.5).¹ The minimal residual disease (MRD) negativity rate by Day 100 from first dose of TECVAYLI^® in evaluable patients was 81 percent.¹

Median duration of response was 22 months (95 percent Confidence Interval [CI], 16-Not Evaluable [NE]) for all responders, and 27 months (95 percent CI, 22-NE) for patients who achieved a CR or better.¹ Median progression-free survival (mPFS) was 11 months (95 percent CI, 9-16) for all patients and was 27 months (95 percent CI, 23-NE) for patients who achieved a CR or better.¹ Median OS was 22 months (95 percent CI, 15-NE) for all patients and was not reached for patients who achieved a CR or better.¹

“After a median of two years’ follow up, it’s encouraging to see sustained and durable responses, particularly in such a difficult-to-treat population with such high unmet medical need,” said Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator.^† “This is the most robust data set to date for teclistamab, and our findings further support the role it can play in the treatment of patients with relapsed or refractory disease.”

The most common Grade 3/4 hematologic adverse events (AEs) were neutropenia (65.5 percent); anemia (37.6 percent); lymphopenia (34.5 percent) and thrombocytopenia (22.4 percent).¹ Infections occurred in 80 percent of patients (55.2 percent Grade 3/4).¹ Incidence and severity of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) did not change during the long term follow-up period.¹ As of data cut-off, AEs leading to dose reduction or discontinuation of TECVAYLI^® treatment were infrequent; there were seven treatment-related deaths observed in the study.¹

Results Suggest Durable Responses with Biweekly Dosing of TECVAYLI^® (Abstract #8034)
Results of an analysis of the investigational use of biweekly (Q2W) or monthly (Q4W) dosing of TECVAYLI^® in the MajesTEC-1 study were also presented, demonstrating sustained deep responses with less frequent dosing in responding patients.² Patients with relapsed or refractory disease who had received at least three prior lines of therapy including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody were initially treated with the recommended Phase 2 dose (RP2D) of 1.5 mg/kg TECVAYLI^® weekly (QW) administered subcutaneously and were able to switch to Q2W dosing if they achieved a confirmed partial response (PR) or better after four or more cycles of treatment (Phase 1) or a confirmed CR or better for six months or longer (Phase 2).² Patients could further switch to Q4W dosing if they demonstrated continued response on the Q2W schedule. Patient responses were assessed per IMWG 2016 criteria.²

As of January 2023, 165 patients had received TECVAYLI^® at the RP2D.² Of 104 responders, 63 patients switched to Q2W and nine patients subsequently switched to Q4W dosing.² Results from the analysis showed that at the time of switch, 85.7 percent of patients had a response of a CR or better, 12.7 percent were in very good partial response (VGPR), and 1.6 percent were in PR.² The median time to switch from QW to Q2W dosing was 11.3 months (range, 3-30). At a median follow-up of 12.6 months (range, 1-25) since switching, the median duration of response was not yet reached, and 68.7 percent (95 percent CI: 53.6-79.7) of patients who switched remained in response for two or more years from the time of first response.² As of data cut-off, 42 of 63 responders maintained a response after switching to less frequent dosing.² The new onset of Grade 3 or higher infections was lower in responders who switched to Q2W or Q4W dosing compared to those who remained on QW dosing (15.6 percent vs. 33.3 percent) and no new safety signals were observed with less frequent dosing.²

These data have been submitted to health authorities globally as part of a regulatory application which, if approved, would allow appropriate patients to receive TECVAYLI^® biweekly.²

“These data suggest less frequent dosing of TECVAYLI may be considered after achieving a response,” said Rachel Kobos, M.D., Vice President, Janssen Oncology Research & Development, LLC. “We remain committed to finding not only innovative treatments for patients in need of new options, but also new strategies for optimizing regimens and reducing side effects during treatment.”

Evaluation of Prophylactic Tocilizumab for the Reduction of Cytokine Release Syndrome (Abstract #8033)
Important new data studying the investigational prophylactic use of tocilizumab (toci), an interleukin-6 receptor inhibitor, for the reduction of CRS in patients treated with TECVAYLI^® were also presented at the meeting.[3] In this prospective exploratory cohort of MajesTEC-1, eligible adult patients with RRMM received subcutaneous TECVAYLI^®.³ Patients were prophylactically dosed with toci (a single 8 mg/kg IV dose) within four hours prior to the first TECVAYLI^® step-up dose, and CRS was graded per Lee Criteria and managed per institutional guidelines.³

Results of the study (n=23) showed that a single dose of toci before TECVAYLI^® treatment reduced the overall incidence of CRS relative to the MajesTEC-1 study, with no evidence of impact on response.³ At a median follow-up of 2.6 months (range, 0.1-7), CRS was 26 percent (all Grade 1 or 2), representing a 2.5 fold reduction in CRS versus the incidence seen in MajesTEC-1, in which prophylactic toci was not employed.³ Median time to onset of CRS was two days, with a median duration of two days.³ All CRS events were managed with toci (one added dexamethasone); all CRS events resolved and no patients discontinued TECVAYLI^® due to CRS.³

About the MajesTEC-1 Study^4,5
MajesTEC-1 (NCT04557098, NCT03145181), is a Phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study to evaluate the safety and efficacy of TECVAYLI^® in adults with relapsed or refractory multiple myeloma who received three or more prior lines of therapy.^4,5

Phase 1 of the study (NCT03145181) was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2).⁵ It evaluated safety, tolerability, pharmacokinetics, and preliminary efficacy of TECVAYLI^® in adult participants with RRMM.⁵ Study criteria for Phase 1 excluded patients who had stroke, seizure, allogeneic stem cell transplantation within the past six months, Eastern Cooperative Oncology Group (ECOG) performance score of 2 or higher, known active central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma, or active or documented history of autoimmune disease, with the exception of vitiligo, Type 1 diabetes, and prior autoimmune thyroiditis.⁵

Phase 2 of the study (NCT04557098) evaluated the efficacy of TECVAYLI^® at the RP2D, established at subcutaneous 1.5 mg/kg weekly, as measured by ORR.⁴ During week one, participants received step-up doses of subcutaneous TECVAYLI^® (0.06 and 0.3 mg/kg).⁴ Subsequently, participants received weekly treatment doses of subcutaneous TECVAYLI^® 1.5 mg/kg until disease progression or unacceptable toxicity.⁴ Efficacy was established based on ORR as determined by the Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) 2016 criteria.⁴

The primary endpoint was ORR or unacceptable toxicity.⁴ Secondary endpoints included duration of response, VGPR, CR, stringent complete response, time to response, minimal residual disease status, progression-free survival, overall survival, safety, pharmacokinetics, immunogenicity and patient-reported outcomes.⁴

As of January 2023, 165 patients in the MajesTEC-1 study were treated with TECVAYLI^® at the recommended subcutaneous RP2D of 1.5 mg/kg preceded by step-up doses of 0.06 and 0.3 mg/kg with the option to switch to dosing once every two weeks (Q2W).⁶ At the data cut-off, 47 patients remained in the study, and 42 of 47 had switched to Q2W dosing and maintained a response.

About TECVAYLI^®
TECVAYLI^® (teclistamab-cqyv) received approval from the U.S. Food and Drug Administration in October 2022 as an off-the-shelf (or ready to use) bispecific antibody that is administered as a subcutaneous treatment for adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.⁶ TECVAYLI^® is the only approved BCMA×CD3 bispecific antibody with a personalized, weight-based dosing schedule for the treatment of triple-class exposed RRMM.⁶

In August 2022, TECVAYLI^® received approval from the European Commission as an off-the-shelf bispecific antibody administered as a subcutaneous treatment for adult patients with RRMM who have received at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.⁷ Teclistamab-cqyv (TECVAYLI^®) was recommended by the National Comprehensive Cancer Network^® (NCCN^®) as a treatment option for these patients.⁸

TECVAYLI^® is a first-in-class, bispecific T-cell engager antibody therapy which uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T cells and to the B cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.⁶

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.⁹ In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.¹⁰ Multiple myeloma is the third most common blood cancer and remains an incurable disease. In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people will die from the disease.¹¹ People living with multiple myeloma have a 5-year relative survival rate of 53 percent. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.¹²

TECVAYLI^® IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

• Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI^®. Initiate treatment with TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI^® until CRS resolves or permanently discontinue based on severity.
• Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI^®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI^® until neurologic toxicity resolves or permanently discontinue based on severity.

TECVAYLI^® is available only through a restricted program called the TECVAYLI^® Risk Evaluation and Mitigation Strategy (REMS).

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome - TECVAYLI^® can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI^® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI^®. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

Initiate therapy according to TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI^® accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI^® based on severity.

TECVAYLI^® is available only through a restricted program under a REMS.

Neurologic Toxicity including ICANS - TECVAYLI^® can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI^® at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI^®.

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI^® at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI^®. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI^® based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI^® step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI^® is available only through a restricted program under a REMS.

TECVAYLI^® REMS - TECVAYLI^® is available only through a restricted program under a REMS called the TECVAYLI^® REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Hepatotoxicity - TECVAYLI^® can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Infections - TECVAYLI^® can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI^® and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Monitor immunoglobulin levels during treatment with TECVAYLI^® and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Neutropenia - TECVAYLI^® can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI^® based on severity.

Hypersensitivity and Other Administration Reactions - TECVAYLI^® can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI^® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI^® and for 5 months after the last dose.

ADVERSE REACTIONS
The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Please read full Prescribing Information including Boxed Warning for TECVAYLI^®.

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 & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at @JanssenUS and @JanssenGlobal. Janssen Research & Development, LLC is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

^†Dr. van de Donk has served as a paid consultant to Janssen; he has not been paid for any media work.

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 Research & Development, LLC, 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 1, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other 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.

[1] Van de Donk N et al. Long-Term Follow-Up From MajesTEC-1 of Teclistamab, a BCMA×CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. 2023 ASCO Annual Meeting – American Society of Clinical Oncology. June 2023.

[2] Usmani S et al. Durability of Responses With Biweekly Dosing of Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma Achieving a Clinical Response in the MajesTEC-1 Study. 2023 ASCO Annual Meeting – American Society of Clinical Oncology. June 2023.

[3] Van de Donk N et al. Evaluation of prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) to inform the management of patients (pts) treated with teclistamab in MajesTEC-1. 2023 ASCO Annual Meeting – American Society of Clinical Oncology. June 2023.

[4] A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). https://clinicaltrials.gov/ct2/show/NCT04557098. Accessed June 2023.

[5] Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). https://clinicaltrials.gov/ct2/show/NCT03145181. Accessed June 2023.

[6] TECVAYLI^® U.S. Prescribing Information. October 2022.

[7] TECVAYLI. European Medicines Agency. www.ema.europa.eu/en/medicines/human/EPAR/tecvayli. Accessed June 2023.

[8] NCCN^® Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Multiple Myeloma V3.2023. National Comprehensive Cancer Network. Accessed June 2023.

[9] Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol.2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178. Accessed June 2023.

[10] National Cancer Institute. Plasma Cell Neoplasms. https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq. Accessed June 2023.

[11] American Cancer Society. "Key Statistics About Multiple Myeloma" Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370%20in%20women). Accessed June 2023.

[12] American Cancer Society. "What Is Multiple Myeloma" Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed June 2023.