TCE Trispecific Antibodies Poised to Challenge CAR-T in Multiple Myeloma

AsMMA senior player in the field, Johnson & Johnson already has5Drug Approved for Marketing, Small Molecule DrugBortezomib, TargetedCD38Monoclonal AntibodyDaratumumab, TargetedBCMATheCAR-TMedicineCarvyktiAnd TargetedBCMA/CD3Bispecific AntibodyTecvayli《The 7th Bispecific Antibody! Johnson & Johnson's BCMA/CD3 Bispecific Antibody Approved for Marketing》，and there is also a targetedGPRC5D/CD3The bispecific antibody 《The 11th Bispecific Antibody: Johnson & Johnson's GPRC5D/CD3 Bispecific Antibody Approved for Marketing》. However, Johnson & Johnson is not content with its current success and continues to upgrade and developBCMA/GPRC5D/CD3Three Antibiotics,BCMA /CD3AndGPRC5D/ CD3Combined Therapy《You have to admit it!》，which is about to be held inASCOAt the conference, Johnson & Johnson announced the clinical efficacy of these two drugs, among whichBCMA/GPRC5D/CD3Three Antibodies inBCMAAndGPRC5D naive Among the patientsORRAchieved100%, and in patients with triple-drug resistance,ORR Up to86% (≥VGPR：75%), with efficacy comparable toCAR-T. In addition,Ichnos GlenmarkAlso announced itsBCMA/CD38/CD3Three AntibioticsPreliminary efficacy:

According to the target announced by Johnson & JohnsonGPRC5D/BCMA/CD3Tri-specific antibody-related patents.JNJ-5322For1+1+1The design allows antibodies to function through two distinct mechanisms.MMTumor damage, as shown in the figure below:1) TargetedBCMAAndGPRC5DTheFabAt the same time, they bind to the same tumor and recruitTCells kill tumors;2) TargetedBCMAAndGPRC5DTheFabCombining different tumor cells and utilizing the sameTCells kill different tumor cells。

This timeASCOAt the meeting, Johnson & Johnson announcedJNJ-5322 (NCT05652335TheⅠPhase Clinical Study, Dose Escalation/The extended queue includesPrevious ContactTreated with proteasome inhibitors, immunomodulatory drugs, and anti-CD38Monoclonal Antibody TherapyTheRRMMPatient. The study explored every two weeks (Q2W) or every four weeks (Q4W) Fixed Subcutaneous Injection Dose Escalation Regimen (0.4-300 mg），Including the proposed recommended Phase II dose (RP2D）100 mg Q4W. The patient is receiving100 mg Q4WReceive one dose before the dosage.5 mgThe stepwise increased dose to reduceCRSRisk.

As of2025Year1Month15Day,126Example: Patient AcceptanceJNJ-5322Treatment (where36Example Acceptance100 mg Q4WDose), median follow-up time (mFU）8.2Months. Median age of patients64Years,Previous median number of treatment lines4Line,100%For the exposure of three drug categories (56%(For refractory)，31%With high-risk cytogenetic abnormalities,23%Previously received anti-BCMA/GPRC5DTreatment (77%(Have not received such treatment)。

In patients whose efficacy can be evaluated,RP2DDose Group (n=36) ofORRFor86%（75%Achieving ≥ Very Good Partial Remission[VGPR]）, Overall Population (n=124）ORRFor73%（66%≥VGPR）。In patients who have not received anti-BCMA/GPRC5DAmong the treated patients (n=27），RP2DDose GroupORRReach100%（89%≥VGPR）, all relieved patients continued to respond (median follow-up8.5months). The median time to first response was1.2Months。

Take another look.Ichnos GlenmarkTheBCMA/CD38/CD3Three AntibioticsISB2001, the antibody also adopts1:1:1Design, and inFcSection IntroductionL234A、L235AAndP329AMutation, RemovalADCCEffect, Additionally, it achieves light chain and heavy chain mismatch through a common light chain.

This Year'sASCOAt the meeting,Ichnos GlenmarkEvaluatedISB2001In relapse/Refractory Multiple Myeloma (RRMM) Pharmacodynamic characteristics in patients. Patients had previously receivedEpidemic regulating drugs, proteasome inhibitors and anti-CD38Treatment, and are resistant or intolerant to existing therapies.Allowing those who have previously receivedBCMATargeted and/OrTPatient Enrollment for Cell-Directed Therapy。ISB 2001Once a weekSubcutaneous injection (SC) method of administration，28A cycle of days, with the initial stepwise increasing dose on day1Day (15 mg/kg), the4DayAdminister different target doses.

24The patient receivedISB2001Treatment, Coverage8A dose level (5–1800 mg/kg), Median follow-up time6Months (Range:2–12）。Currently enrolling the highest dose groupDL9（2700 mg/kg）。Previous median number of treatment lines6Line（3-11）All patients have received treatment with three types of drugs.71%（17/24) Have received five categories of drugs, among which18%（3/17) Resistance to five types of drugs.

Efficacy: Overall Response Rate (ORR) for75%, including: stringent complete remission (sCR) for13%, Complete Remission (CRFor)13%，VGPRFor38%，PRFor13%`, from as low as`50 mg/kgThe dose level at which relief was observed (1Example: Patient AchievementMRDNegativesCR），In ≥50 mg/kgIn the dose group,ORRReach82%；

Safety: Not observedDLT、Adverse events leading to discontinuation of the drug (AE) or death cases.33%（8Example) The patient reported severeAE。54%（13Example) The patient presented with3-4Drug-relatedAE。Cytokine Release Syndrome (CRS) Incidence rate is70.8%（17Example), mainly for1-2Level, Median time to onset is3Day, median duration is2Day.Not observedNeurotoxicityAEOr Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS）。

By contrast, Legend Biotech'sBCMA CAR-TTherapy at2024Year8Approved in China this month, based on a multicenter confirmatory Phase II clinical study conducted in China.CARTIFAN-1（NCT03758417). Median follow-up37.29The efficacy evaluation results after several months showed that those receivingCilta-celAnalysis of the Effectiveness of Injection Treatment58Among the patients,Overall Response Rate (ORR) Reach87.9%, Very good partial remission (VGPR) and above reached86.2%, Complete Remission (CR`) or in the strict sense, complete remission (`sCR) Reach79.3%, Median Duration of Response (mDOR) for32.56months, median progression-free survival (mPFS) for30.13Months, Median Overall Survival (mOS) Not reached. The patient population is the same, having received at least three lines of therapy (including at least one proteasome inhibitor and at least one immunomodulatory agent).

Therefore,Johnson & Johnson's Three Antibodies inRP2DDose Group (n=36) ofORRFor86%（75%Achieving ≥ Very Good Partial Remission[VGPR]), basically already andCAR-TTherapyCilta-cel is equivalent, andIn patients who have not received anti-BCMA/GPRC5DAmong the treated patients (n=27），RP2DDose GroupORRUp to100%（89%≥VGPR), superior to all current therapies. In view of the accessibility and cost of bispecific antibodies, inMMField,TCEThree Antibiotics Will Definitely Have an Impact onCAR-TCause a certain impact。

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