Phase 3 Randomized Study of JNJ-79635322 Versus Teclistamab in Relapsed or Refractory Multiple Myeloma After Prior PI, IMiD, and Anti-CD38 Therapy
- Trial ID
- 2025-522007-18-00
- Protocol
- 79635322MMY3001
- Sponsor
- Janssen Cilag International
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to compare the efficacy of JNJ-79635322 with a BCMAxCD3 bispecific antibody in relapsed or refractory multiple myeloma, which is clinically relevant for assessing antitumor activity in a heavily pretreated population. The secondary objectives are to further compare efficacy, to evaluate and characterize the overall safety profile of JNJ-79635322, to assess health-related quality of life, symptoms, and functioning through patient-reported outcome tools, to assess tolerability from the participant perspective, to characterize pharmacokinetics, and to assess immunogenicity.
Participants
The trial enrolled 265 participants with relapsed or refractory multiple myeloma. The study population included male and female patients and required an age of 18 years or older. Participants were selected from individuals with documented multiple myeloma meeting International Myeloma Working Group diagnostic criteria, measurable disease at screening, and prior treatment exposure of at least three antimyeloma regimens, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Eligible participants had relapsed or refractory disease, an ECOG performance status of 0 to 2, and adequate renal, hepatic, and hematologic function. Participants were also required to provide informed consent and to be willing and able to adhere to specified lifestyle restrictions. Relevant restrictions included agreement not to breastfeed, not to donate gametes, and to use effective contraception during study treatment and for 6 months after the last dose. The sponsor did not provide information on specific diet, physical activity, or other habitual lifestyle characteristics of the enrolled population.
Plans and Procedures
The study is a Phase 3 randomized controlled trial comparing JNJ-79635322 with an anti-BCMAxCD3 bispecific antibody in participants with relapsed or refractory multiple myeloma. The main objective is to compare efficacy, with dual primary endpoints of overall response rate and progression-free survival. Study participation begins with a screening visit to confirm eligibility, including disease status, prior therapy requirements, performance status, and laboratory criteria. This is followed by study treatment administration and scheduled follow-up visits for assessment of efficacy, safety, laboratory parameters, pharmacokinetics, immunogenicity, and patient-reported outcomes. An end-of-study visit is performed at the conclusion of participation to complete final evaluations. The overall trial is planned from 2026-05-14 to 2031-09-30, and participant involvement is expected to continue through the treatment and follow-up period defined by the protocol. Early termination may occur if eligibility criteria are no longer met, if study treatment is discontinued, or if disease progression, unacceptable toxicity, or other protocol-defined reasons lead to withdrawal from the study.
Treatment
JNJ-79635322 was administered as a solution for injection by subcutaneous route. It was evaluated as the investigational treatment in the study. The source data do not provide the dose, dosing frequency, or dosing schedule. The study also included duplicate entries for this product in the source data.
teclistamab was administered as a solution for injection by subcutaneous route. It served as the comparator treatment in the study. The source data do not provide the dose, dosing frequency, or dosing schedule. The study also included duplicate entries for this product in the source data.
Efficacy
Efficacy will be assessed by dual primary endpoints of overall response rate and progression-free survival. Secondary efficacy evaluations will include very good partial response or better, complete response or better, duration of response, minimal residual disease-negative complete response, minimal residual disease-negative complete response at 9 months, sustained minimal residual disease-negative complete response with duration of at least 12 months, progression-free survival 2, overall survival, and time to next treatment. Additional efficacy assessments will examine change from baseline in health-related quality of life, symptoms, and functioning using the MySIm-Q, EORTC QLQ-C30, and EQ-5D-5L scores, time to worsening in these measures, and the proportion of participants with meaningful improvement in these measures. Side effect burden will also be evaluated using the EORTC IL46.
Assessment methods will include the use of the listed score-based instruments for health-related quality of life, symptoms, and functioning, together with the specified response and survival endpoints. No further schedule or measurement details are provided.
Inclusion and Exclusion Criteria
Inclusion Criteria
- At the time of informed consent, be ≥18 years of age (or at least the legal age of majority in the jurisdiction in which the study is taking place).
- 2.1 Documented diagnosis of MM as defined by the criteria below: a. MM diagnosis according to the IMWG diagnostic criteria (Rajkumar 2014). b. Measurable disease at screening as assessed by central laboratory, defined by any of the following: i. Serum M-protein level ≥0.5 g/dL ii. Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio iii. Urine M-protein level ≥200 mg/24 hours NOTE: In exceptional circumstances and after discussion with and written approval by the sponsor, local laboratory results may be used to determine initial eligibility, but only if the local results are clearly (≥25%) above the thresholds for measurability. In such cases, central laboratory results should still be obtained from samples collected prior to the start of study treatment to establish baseline values and confirm the results from the local laboratory.
- Received at least 3 prior lines of antimyeloma therapy including a PI, an IMiD, and an anti-CD38 antibody. Refer to Section 10.7 for the definition of a line of therapy.
- Documented evidence of PD or failure to achieve a response (ie, PR or better) to the last line of therapy based on investigator’s determination of response by the IMWG criteria. Relapsed or refractory disease as defined below: a. Relapsed disease is defined as an initial response to prior treatment, followed by confirmed PD by the IMWG response criteria >60 days after cessation of treatment. b. Refractory disease is defined as failure to achieve a response (ie, PR or better) or confirmed PD by the IMWG response criteria during previous treatment or ≤60 days after cessation of treatment
- Have discontinued concurrent use of any other anticancer treatment (including nonpalliative radiotherapy) or investigational agent. Toxicity related to previous anticancer therapy must have resolved to resolved to Grade 1 or better (except alopecia, skin fibrosis or discoloration, dry mouth, endocrinopathy managed with replacement therapy, peripheral neuropathy, and dysgeusia, which must be Grade 2 or better).
- Have an ECOG performance status score of 0 to 2 at screening and immediately before the start of study treatment administration (Oken 1982).
- 7.1 Renal function: Have an eGFR, calculated with the CKD-epi creatinine formula (Section 10.12) of >30 mL/min during the screening period.
- Hepatic function: Participants are eligible if they have the following laboratory values during the screening period and within 1 day of the start of administration of study treatment: AST and ALT <2.5×ULN Total bilirubin <1.5×ULN Bilirubin in case of known congenital nonhemolytic hyperbilirubinemias such as Gilbert’s Syndrome: isolated total bilirubin ≥1.5×ULN with direct bilirubin <1.5×ULN
- Hematologic values: Participants are eligible if they have the following laboratory values during the screening period and within 1 day of the start of administration of study treatment: Hemoglobin ≥7.5 g/dL, without use of transfusion or growth factors within 7 days Neutrophils ≥0.75×103/μL (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated G-CSF prior to the laboratory test) Platelets ≥50×103/μL, without use of transfusion or growth factors within 7 days
- Participants must agree, while on study treatment and for 6 months after the last dose of study treatment, to: Not breastfeed or be pregnant. Not donate gametes (ie, eggs or sperm) or freeze for future use for the purposes of assisted reproduction. Wear an external condom, when transmission of sperm/ejaculate can occur. If of childbearing potential, Have a negative highly sensitive (eg, β-hCG) pregnancy test at screening and within 24 hours before the first dose of study treatment, and agree to further pregnancy tests, Practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used. If able to produce sperm and their partner is of childbearing potential, the partner must practice a highly effective method of contraception. See Section 10.3 for details.
- 11.Must provide informed consent as described in Section 10.2.3.
- Be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Exclusion Criteria
- Serious underlying medical conditions, such as: a. Evidence of active systemic viral, fungal, or bacterial infection requiring systemic antiviral, antifungal, or antimicrobial therapy and clinically relevant at the time of first dose. b. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment. EXCEPTION: Participants with vitiligo, type I diabetes, or prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed or treatment. c. Overt clinical evidence of dementia or altered mental status d. Any of the following within 6 months prior to first dose of study treatment: severe or unstable angina, myocardial infarction, seizure, major thromboembolic events (eg, pulmonary embolism, cerebrovascular accident [including TIA and stroke]), clinically significant ventricular arrhythmias or heart failure New York Heart Association functional classification Class III to IV. Uncomplicated deep vein thrombosis is not considered exclusionary.
- Active hepatitis of infectious origin. a. Seropositive for hepatitis B: defined by a positive test for HBsAg. Participants with resolved infection (ie, participants who are HBsAg negative with positive antibodies to total hepatitis B core antigen [anti-HBc])must be screened using RT-PCR measurement of HBV-DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV-DNA by RT-PCR. (see Section 10.6, Hepatitis B Virus Screening) b. Known hepatitis C infection or positive serologic testing for hepatitis C virus (anti-HCV) antibody. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained at screening or within 3 months prior to first dose of study treatment. c. Other clinically active liver disease of infectious origin.
- 3.Participants who are HIV-positive and meet any of the following: a. Detectable viral load (ie, ≥50 copies/mL) at screening b. CD4+ count ≤300 cells/mm3 at screening c. Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening d. Receive treatment other than continued HAART. A change in HAART due to resistance/progression must occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening. Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment).
- 4.Plasma cell leukemia at the time of screening (≥5% circulating PCs in peripheral blood smear), Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light chain amyloidosis.
- Known active or prior CNS involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain MRI and lumbar cytology are required.
- 6.1 Presence of any of the following: i. Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM). ii. Any history of malignancy, other than MM, that is considered at high risk of recurrence requiring systemic therapy. The only allowed exceptions are: i. Any malignancy that was not progressing nor requiring treatment change in the last 12 months and not considered at high risk or recurrence requiring systemic therapy. ii. Malignancies treated within the last 12 months and considered at very low risk of recurrence: a. Non-muscle invasive bladder cancer (solitary Ta-papillary urothelial neoplasm of low malignant potential or low-grade, <3 cm, no carcinoma in situ) b.Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone c. Non-invasive cervical cancer d. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer (anti-hormonal therapy is permitted) e. Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (Radical Prostatectomy/Radiotherapy/focal treatment) iii. Other malignancy that is considered cured with minimal risk of recurrence NOTE: In the event of any questions, consult with the sponsor prior to enrolling a participant.
- 7.Suspected or known allergies, hypersensitivity, or intolerance to the excipients of JNJ-79635322 (refer to the IB).
- 8.1 Major surgery, (eg, requiring general anesthesia) within 2 weeks before first dose, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
- Suspected or known allergies, hypersensitivity, or intolerance to teclistamab or its excipients (TECVAYLI USPI 2024).
- 1 Prior or concurrent exposure to any of the following, in the specified time frame prior to randomization: a. T-cell redirection therapy (eg, CAR-T, bispecific antibody) within 6 months. b. History of receiving both BCMA and GPRC5D-directed therapy c. History of receiving a BCMA-directed bispecific antibody d. An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks before the start of study treatment administration without signs of graft-versus-host disease. e. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14 days prior to first dose of study drug. f. Treatment with an investigational drug, investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 28 days or ≥5 half-lives, whichever is longer.
- Received or plans to receive any live, attenuated vaccine within 4 weeks before the first dose of study treatment, during, or within 90 days after the last dose of study treatment. Non-live and non-replication-competent vaccines approved or authorized for emergency use by local health authorities are allowed.
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 14 May 2026 | 26 |
 Germany | Recruiting | 14 May 2026 | 11 |
 Greece | Recruiting | 14 May 2026 | 16 |
 Italy | Recruiting | 14 May 2026 | 37 |
 The Netherlands | Recruiting | 14 May 2026 | — |
 Norway | Recruiting | 14 May 2026 | 15 |
 Spain | Recruiting | 14 May 2026 | 26 |
| Netherlands | — | — | 26 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
teclistamab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 999 | PRD9936206 |
JNJ-79635322 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 999 | PRD10228220 |
teclistamab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 999 | PRD9936207 |
JNJ-79635322 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 999 | PRD10228219 |