Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma ALNUCTAMAB
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What's the purpose of this trial?

Study CC-93269-MM-001 is an open-label, Phase 1, dose escalation (Part A and C) and expansion (Parts B and D), first-in-human clinical study of CC-93269 in subjects with relapsed and refractory multiple myeloma.

This trial has temporarily put patient recruitment on hold.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
  2. Subject (male or female) is ≥ 18 years of age the time of signing the ICF.
  3. Subject has non-secretory multiple myeloma, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, or amyloidosis.
  4. Subjects must have measurable disease (as determined by the central lab).
  5. Subject consents to hospitalization for monitoring and collection of study peripheral blood samples.
  6. Subject consents to serial bone marrow aspirations and/or biopsies during Screening, study treatment and at the end of treatment.
  7. Subject has an Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
  8. Subjects must have adequate hematologic, liver, renal, and coagulation function as assessed by laboratory tests.
  9. Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and during the safety follow-up period.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

 

  1. Subject has received prior therapy directed at B cell maturation antigen (BCMA).
  2. Subject has symptomatic central nervous system involvement of multiple myeloma.
  3. Subject has non-secretory multiple myeloma, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis.
  4. Subject is on chronic systemic immunosuppressive therapy or corticosteroids.
  5. Subjects with clinically significant cardiac disease.
  6. Subject had a prior autologous stem cell transplant ≤ 3 month prior to starting CC-93269.
  7. Subject had a prior allogeneic stem cell transplant ≤ 12 month prior to starting CC-93269.
  8. Subject had a prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting CC-93269, whichever is shorter. Subjects must have recovered from any clinically significant non-hematologic toxicities (ie, to Grade ≤1) of prior systemic anti-cancer directed treatments unless otherwise specified
  9. Subject had major surgery ≤ 2 weeks prior to starting CC-93269.
  10. Subject is a pregnant or lactating female.
  11. Subject has known history or serologic evidence of human immunodeficiency virus (HIV) infection.
  12. Subject has known history, virologic or serological evidence of hepatitis B or C virus (HBV/HCV) infection. Subjects who had HCV but have received an antiviral treatment and show no detectable HCV viral RNA for 6 months are eligible
  13. Subject has a history of a venous thromboembolic event (VTE) within 6 months prior to study entry (eg, deep-vein thrombosis or pulmonary embolism). Subjects with distant history of VTE (ie, occurring > 6 months prior to study entry) who require ongoing treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors) are eligible for study entry.
  14. Subject has a history of concurrent second cancers requiring active, ongoing systemic treatment.
  15. Subject has a history or presence of clinically relevant central nervous system (CNS) pathology.
  16. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  17. Subject has any condition (eg, active or uncontrolled infection) including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. .
  18. Subject has any condition that confounds the ability to interpret data from the study.
  19. Subject has inadequate pulmonary function.
  20. Subject has active, uncontrolled, or suspected infection.
  21. Subject has pulmonary, cardiac, or hepatic involvement of extramedullary multiple myeloma.
  22. Subjects with a history of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
  23. Recent SARS-CoV-2 vaccine as specified in the protocol.

Additional Trial Information

Phase 1

Enrollment: 220 patients (estimated)

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Published Results

Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study

December 10, 2022

At data cutoff on May 31, 2022, 70 pts have received IV ALNUC, 39% (27/70) achieved an objective response, and median progression-free survival was 13.3 wks (95% CI, 8.1–23.9). Median DOR in pts achieving a response with IV ALNUC was 146.1 wks (95% CI, 40.6–not reached).

Forty-seven pts were treated with SC ALNUC in dose escalation (10 mg: n = 6; 15 mg: n = 4; 30 mg: n = 6; 60 mg: n = 3) and dose expansion (10 mg: n = 19; 30 mg: n = 9). Median age was 63 yrs; 55% were female. Pts received a median of 4 prior regimens; 98% had myeloma refractory to the last LOT, 96%/62% had triple-class exposed/refractory myeloma, and 60%/21% had penta-drug exposed/refractory myeloma. At the May 31, 2022 data cutoff, median duration of follow-up was 2.6 mo (range, 0–11.4), and 68% (n = 32) of pts were continuing SC ALNUC treatment.

Any-grade/grade 3–4 treatment-emergent adverse events occurred in 89%/62% of treated pts; the most common were CRS (53%/0%), neutropenia (34%/30%), and anemia (34%/17%). All CRS events were limited to grade 1 (21 pts; 45%) or grade 2 (4 pts; 9%); 20 pts received ≥ 1 concomitant medication for CRS, including tocilizumab (n = 12) and/or corticosteroids (n = 8). Median time to CRS onset was 3 d (range, 1–20); median duration was 2 d (range, 1–11). In 16 pts with grade 3–4 neutropenia, median time to resolution (grade ≤ 2) was 6 d (range, 1–36). There was one grade 1 immune effector cell-associated neurotoxicity event. No pts discontinued treatment due to adverse events; no treatment-related deaths occurred.

Preliminary population pharmacokinetic analysis estimated SC ALNUC bioavailability of ~70%; 30 mg SC achieved similar concentrations observed with 10 mg IV Cmax by end of C1; baseline body weight was not a significant covariate of exposure. Hallmark pharmacodynamic effects of TCEs were observed with SC and IV ALNUC (peripheral blood immune cell redistribution, transient cytokine release, and induction of T-cell factors associated with antitumor activity).

Among 41 efficacy-evaluable (EE) pts treated with SC ALNUC (received ≥ 1 dose and had ≥ 1 post-baseline disease assessment), ORR was 51% (21/41 pts) across all dosing regimens and 77% (10/13 pts) in pts receiving target doses ≥ 30 mg (Figure). Among the 21 pts who achieved a response, 14 pts had evaluable MRD samples, and all (100%) were MRD negative (10-5 sensitivity) at C2D1 or C4D1. Median time to response was 4.3 wks (range, 4.1–17.4), and all 21 responses (100%) were ongoing.

Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study

May 31, 2022

At data cutoff on May 31, 2022, 70 pts have received IV ALNUC, 39% (27/70) achieved an objective response, and median progression-free survival was 13.3 wks (95% CI, 8.1–23.9). Median DOR in pts achieving a response with IV ALNUC was 146.1 wks (95% CI, 40.6–not reached).

Forty-seven pts were treated with SC ALNUC in dose escalation (10 mg: n = 6; 15 mg: n = 4; 30 mg: n = 6; 60 mg: n = 3) and dose expansion (10 mg: n = 19; 30 mg: n = 9). Median age was 63 yrs; 55% were female. Pts received a median of 4 prior regimens; 98% had myeloma refractory to the last LOT, 96%/62% had triple-class exposed/refractory myeloma, and 60%/21% had penta-drug exposed/refractory myeloma. At the May 31, 2022 data cutoff, median duration of follow-up was 2.6 mo (range, 0–11.4), and 68% (n = 32) of pts were continuing SC ALNUC treatment.

Any-grade/grade 3–4 treatment-emergent adverse events occurred in 89%/62% of treated pts; the most common were CRS (53%/0%), neutropenia (34%/30%), and anemia (34%/17%). All CRS events were limited to grade 1 (21 pts; 45%) or grade 2 (4 pts; 9%); 20 pts received ≥ 1 concomitant medication for CRS, including tocilizumab (n = 12) and/or corticosteroids (n = 8). Median time to CRS onset was 3 d (range, 1–20); median duration was 2 d (range, 1–11). In 16 pts with grade 3–4 neutropenia, median time to resolution (grade ≤ 2) was 6 d (range, 1–36). There was one grade 1 immune effector cell-associated neurotoxicity event. No pts discontinued treatment due to adverse events; no treatment-related deaths occurred.

Preliminary population pharmacokinetic analysis estimated SC ALNUC bioavailability of ~70%; 30 mg SC achieved similar concentrations observed with 10 mg IV Cmax by end of C1; baseline body weight was not a significant covariate of exposure. Hallmark pharmacodynamic effects of TCEs were observed with SC and IV ALNUC (peripheral blood immune cell redistribution, transient cytokine release, and induction of T-cell factors associated with antitumor activity).

Among 41 efficacy-evaluable (EE) pts treated with SC ALNUC (received ≥ 1 dose and had ≥ 1 post-baseline disease assessment), ORR was 51% (21/41 pts) across all dosing regimens and 77% (10/13 pts) in pts receiving target doses ≥ 30 mg (Figure). Among the 21 pts who achieved a response, 14 pts had evaluable MRD samples, and all (100%) were MRD negative (10-5 sensitivity) at C2D1 or C4D1. Median time to response was 4.3 wks (range, 4.1–17.4), and all 21 responses (100%) were ongoing.

Interim results from the first study of CC-93269 in patients with relapsed/refractory multiple myeloma

January 22, 2020

  • The overall response rate (ORR) in all patients was 43.3% with a stringent complete response/complete response (sCR/CR) of 16.7%
  • The likelihood of response was dose-dependent. ORR by CC-93269 dose:
    • Dose ≤ 3mg (n= 7): 0%
    • Dose 3 to 6 mg or fixed-dose 6 mg (n= 14): 7%
    • Dose 6 to 10 mg or fixed-dose 10 mg (n= 9): 88.9%
  • Among the nine patients treated with 10 mg of CC-93269, the ORR was 88.9% with a sCR/CR of 44.4%
  • The median time to response was 4.1 weeks (range; 4–13.1)
  • Among 13 responding patients, 11 responses are ongoing
  • Measurable residual disease (MRD) negativity was achieved by 12 of the 13 responding patients

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

Alabama

University of Alabama at Birmingham O'Neal Comprehensive Cancer Center at UAB

Birmingham, AL

Recruitment on Hold

California

UCSF Helen Diller Comprehensive Cancer Center University of California San Francisco

San Francisco, CA

Recruitment on Hold

Connecticut

Yale Cancer Center Smilow Cancer Hospital at Yale-New Haven

New Haven, CT

Recruitment on Hold

Georgia

Winship Cancer Institute of Emory University

Atlanta, GA

Recruitment on Hold

Massachusetts

Massachusetts General Hospital

Boston, MA

Recruitment on Hold

Beth Israel Deaconess Medical Center

Boston, MA

Recruitment on Hold

Washington

Swedish - Cherry Hill Campus Cherry Hill Campus

Seattle, WA

Recruitment on Hold
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