A Phase 3 Study Comparing JNJ-79635322 and an anti-BCMAxCD3 Bispecific Antibody in Participants with Relapsed or Refractory Multiple Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 May 2026 → ongoing

Decision date (initial)

2026-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of JNJ-79635322 with a BCMAxCD3 bispecific antibody.

Secondary objectives 6

1. To further compare the efficacy of JNJ-79635322 with a BCMAxCD3 bispecific antibody
2. To evaluate and characterize the overall safety profile of JNJ-79635322
3. To assess participants’ HRQoL, symptoms, and functioning through various PRO tools
4. To assess participants’ tolerability through PRO
5. To characterize the PK of JNJ-79635322
6. To assess the immunogenicity of JNJ-79635322

Conditions and MedDRA coding

Relapsed or Refractory Multiple Myeloma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. 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. 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.
3. 3. 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.
4. 4. 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
5. 5. 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).
6. 6. Have an ECOG performance status score of 0 to 2 at screening and immediately before the start of study treatment administration (Oken 1982).
7. 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.
8. 8. 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
9. 9. 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
10. 10. 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. 11.Must provide informed consent as described in Section 10.2.3.
12. 12. Be willing and able to adhere to the lifestyle restrictions specified in this protocol.

Exclusion criteria 12

1. 1. 2. 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.
2. 2. 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. 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. 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.
5. 5. 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. 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. 7.Suspected or known allergies, hypersensitivity, or intolerance to the excipients of JNJ-79635322 (refer to the IB).
8. 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.
9. 9. Suspected or known allergies, hypersensitivity, or intolerance to teclistamab or its excipients (TECVAYLI USPI 2024).
10. 10. 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.
11. 11. 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.
12. 12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Dual primary endpoints: overall response rate, progression-free survival

Secondary endpoints 6

1. "VGPR or better CR or better Duration of response MRD-negative CR MRD-negative CR at 9 months Sustained MRD-negative CR (duration ≥12 months) PFS2 OS TTNT"
2. TEAE incidence and severity, laboratory results, and other safety parameters
3. Change from baseline in HRQoL, symptoms, and functioning using the MySIm-Q, EORTC QLQ-C30, and EQ-5D-5L scores Time to worsening in HRQoL, symptoms, and functioning using the MySIm-Q, EORTC QLQ-C30, and EQ-5D-5L scores Percent of participants with meaningful improvement in HRQoL symptoms, and functioning using the MySIm-Q, EORTC QLQ-C30, and EQ-5D-5L scores
4. Proportion of participants who report side effects burden on the EORTC IL46
5. JNJ-79635322 serum concentration
6. Presence of ADAs and neutralizing antibodies to JNJ-79635322

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Cilag International

Sponsor organisation

Janssen Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Third parties 7

Locations

7 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 74 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications