A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide for Multiple Myeloma, Newly Diagnosed AL Amyloidosis, and High-risk Smoldering Multiple Myeloma or JNJ-79635322 in Combination With Pomalidomide for Multiple Myeloma

Browse trials for

• Multiple Myeloma 3,626
• Smoldering Multiple Myeloma 101
• Immunoglobulin Light-chain Amyloidosis 166

Eligibility criteria

Study arms

• Experimental
  Treatment Regimen A and C: JNJ-79635322+Daratumumab

  Participants who have received 1-3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) (Treatment regimen A1 and A3) will receive JNJ-79635322 along with daratumumab to establish the recommended phase 2 doses (RP2D\[s\]) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Based on the study evaluation team (SET) decision, enrollment may proceed in participants with newly diagnosed multiple myeloma (NDMM) (Treatment regimens A2, A4 and C). Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.

  Drug: JNJ-79635322 · Drug: Daratumumab

• Experimental
  Treatment Regimen B: JNJ-79635322+Pomalidomide

  Participants who have received greater than or equal to (\>=)1 prior line of therapy, including a PI and lenalidomide, and are lenalidomide refractory or \>=2 prior lines of therapy, including a PI and lenalidomide will receive JNJ-79635322 along with pomalidomide to establish the RP2D(s) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.

  Drug: JNJ-79635322 · Drug: Pomalidomide

• Experimental
  Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination

  Participants with NDMM will receive JNJ-79635322 along with daratumumab and lenalidomide to establish the RP2D\[s\] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.

  Drug: JNJ-79635322 · Drug: Daratumumab · Drug: Lenalidomide

• Experimental
  Treatment Regimen F: JNJ-79635322 + Daratumumab

  Participants with newly diagnosed amyloid light chain (ND AL) amyloidosis will receive JNJ-79635322 in treatment regimen F along with daratumumab to establish the RP2D\[s\] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 and daratumumab at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.

  Drug: JNJ-79635322 · Drug: Daratumumab

• Experimental
  Treatment Regimen G: JNJ-79635322 + Daratumumab

  Participants with high-risk smoldering multiple myeloma (SMM) will receive JNJ-79635322 in treatment regimen G along with daratumumab to establish the RP2D\[s\] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 and daratumumab at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.

  Drug: JNJ-79635322 · Drug: Daratumumab

Interventions

• DrugJNJ-79635322

  JNJ-79635322 will be administered subcutaneously.

• DrugDaratumumab

  Daratumumab will be administered subcutaneously.

• DrugPomalidomide

  Pomalidomide will be administered orally.

• DrugLenalidomide

  Lenalidomide will be administered orally.

Primary outcomes

1. Part 1: Number of Participants with Dose-limiting Toxicity (DLT)

   DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

   Time frame: Up to 28 days

2. Number of Participants with Adverse Events (AEs) by Severity

   An AE is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event.

   Time frame: Up to 3 Years and 3 months

3. Number of Participants with Clinically Significant Laboratory Abnormalities

   Participants with clinically significant laboratory abnormalities (hematology and chemistry) will be reported.

   Time frame: Up to 3 Years and 3 months

Secondary outcomes

1. Percentage of Participants With Overall Response Rate

   Overall response rate is defined as percentage of participants with newly diagnosed multiple myeloma (NDMM), relapsed or refractory multiple myeloma (R/R MM), or high-risk smoldering multiple myeloma (SMM) who have a partial response (PR) or better evaluated by the investigator as per international myeloma working group (IMWG) 2016 criteria.

   Time frame: Up to 3 Years and 3 months

2. Percentage of Participants With Very Good Partial Response (VGPR) or Better Response Rate

   VGPR or better response rate is defined as the percentage of participants with NDMM, R/R MM, or high-risk SMM who achieve a VGPR or better response (stringent complete response \[sCR\]+ complete response \[CR\]+VGPR) according to the IMWG 2016 criteria.

   Time frame: Up to 3 Years and 3 months

3. Percentage of Participants With CR or Better Response Rate

   CR or better response rate is defined as the percentage of participants with NDMM R/R MM, or high-risk SMM who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria.

   Time frame: Up to 3 Years and 3 months

4. Percentage of Participants With sCR or Better Response Rate

   sCR rate is defined as the percentage of participants with NDMM R/R MM, or high-risk SMM who achieve an sCR according to the IMWG 2016 criteria.

   Time frame: Up to 3 Years and 3 months

5. Duration of Response (DOR)

   DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), as per IMWG 2016 response criteria, or death due to progression, whichever occurs first in participants with NDMM, R/R MM, or high-risk SMM.

   Time frame: Up to 3 Years and 3 months

6. Time to Response (TTR)

   TTR is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participants with NDMM, R/R MM, or high-risk SMM has met all criteria for PR or better as defined by IMWG 2016 response criteria.

   Time frame: Up to 3 Years and 3 months

7. Percentage of Participants With Hematologic Response As Defined by International Amyloidosis Consensus Criteria

   Hematologic response is defined as percentage of participants with newly diagnosed amyloid light chain (ND AL) amyloidosis who achieve complete response, very good partial response, partial response, no response and progression as defined by International amyloidosis consensus criteria present in the protocol will be reported.

   Time frame: Up to 3 Years and 3 months

8. DOR as Defined by International Amyloidosis Consensus Criteria

   DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), as per International amyloidosis consensus criteria, or death due to progression, whichever occurs first in participants with ND AL amyloidosis.

   Time frame: Up to 3 Years and 3 months

9. TTR as Defined by International Amyloidosis Consensus Criteria

   TTR is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant with ND AL amyloidosis has met all criteria for PR or better as defined by International amyloidosis consensus criteria.

   Time frame: Up to 3 Years and 3 months

10. Serum Concentration of JNJ-79635322 and Daratumumab

    Serum samples will be analyzed to determine concentrations of JNJ-79635322 and daratumumab.

    Time frame: Up to 3 Years and 3 months

11. Area Under the Serum Concentration Time Curve from Time Zero to Infinity (AUCinf) for JNJ-79635322 and Daratumumab

    AUCinf for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

12. Area Under the Serum Concentration Time Curve from Time Zero to the Last Measurable Concentration [AUC(0-t)] for JNJ-79635322 and Daratumumab

    AUC(0-t) for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

13. Area Under the Serum Concentration Time Curve During the Dosing Interval (AUCtau) for JNJ-79635322 and Daratumumab

    AUCtau for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

14. Maximum Serum Concentration (Cmax) for JNJ-79635322 and Daratumumab

    Cmax for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

15. Half Life (T1/2) for JNJ-79635322 and Daratumumab

    T1/2 for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

16. Time to Reach Cmax (Tmax) for JNJ-79635322 and Daratumumab

    Tmax for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

17. Systemic Clearance (CL/F) for JNJ-79635322 and Daratumumab

    CL/F for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

18. Apparent Volume of Distribution at Steady State (Vss/F) for JNJ-79635322 and Daratumumab

    Vss/F for JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

19. Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322 and Daratumumab

    Participants with anti-drug antibodies to JNJ-79635322 and daratumumab will be reported.

    Time frame: Up to 3 Years and 3 months

Publications

• Pillarisetti K, Yang D, Luistro L, Yao J, Smith M, Vulfson P, Testa JS, Ponticiello R, Brodeur S, Heidrich B, Packman K, Singh S, Attar R, Elsayed Y, Philippar U. Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. Blood. 2026 Feb 19;147(8):834-847. doi: 10.1182/blood.2025030027. PubMed 41100731 ↗

Individual participant data

Plan to share: Yes — The data sharing policy of Johnson \& Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/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