A study to assess the efficacy and safety of bb2121 in people who have Myeloma that is not responsive after treatment or who had Myeloma which has returned after a period of treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Jan 2019 → 15 Jan 2026

Decision date (initial)

2024-02-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Celgene Corporation US

External identifiers

EU CT number

2023-505183-10-00

EudraCT number

2018-000264-28

ClinicalTrials.gov

NCT03601078

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy, Pharmacogenomic, Pharmacodynamic

The primary objective of the study is to evaluate the efficacy of bb2121, of bb2121in combination with lenalidomide maintenance, and of bb2121 with talquetamab as bridging therapy

Secondary objectives 6

1. Evaluate additional efficacy parameters of bb2121
2. Characterize the expansion and persistence of chimeric antigen receptor (CAR) + T cells, in the peripheral blood (cellular kinetics-pharmacokinetics [PK])
3. Evaluate the development of an anti-CAR antibody response
4. Evaluate changes in health-related quality of life (HRQoL)
5. Cohort 3 only: Evaluate additional efficacy parameters of bb2121 in combination with lenalidomide maintenance
6. Cohort 3 only: Evaluate feasibility of initiating lenalidomide maintenance therapy post-bb2121 infusion

Conditions and MedDRA coding

Relapsed and refractory multiple myeloma (RRMM), multiple myeloma (MM) with progression within 18 months of initial treatment/ or newly diagnosed multiple myeloma (NDMM) with suboptimal response post autologous stem cell transplant (ASCT) (Cohort 3 only)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
2. Cohorts 1 and 2 only, subject has measurable disease, defined as:∙ M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or ∙ Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
3. Subjects with one of the following cohort specific requirements: Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens: • Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen • Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen • Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody • Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen • Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen Cohort 2 subjects with 1 prior anti-myeloma treatment regimen: • Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen • Subject must have the following HR factors: Early relapse defined as: ▪ Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance ▪ Cohort 2b: PD < 18 months since date of start of initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone ▪ Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem) AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance
4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
5. Subject must have recovery to Grade 1 or baseline of any nonhematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy
6. Subject must have adequate vascular access for leukapheresis
7. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
8. Subject is willing and able to adhere to the study visit schedule and other protocol requirements as well as agrees to continued follow up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials
9. Female subjects of childbearing potential (FCBP3) must: • Have a negative pregnancy test(s) as verified by the Investigator, prior to the first dose of study treatment. This applies even if the subject practices true abstinence from heterosexual contact: -All subjects who receive LD chemotherapy/bb2121: Have negative pregnancy tests as verified by the Investigator, prior to LD chemotherapy. • Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with highly effective measures of contraception without interruption, from screening through at least 1 year following LD chemotherapy. Contraception for FCBP must include highly effective methods of contraception from screening until -All subjects receiving LD chemotherapy/bb2121: until at least 1 year following LD chemotherapy. • Agree to abstain from breastfeeding during study participation for at least 1 year following LD chemotherapy. • Refrain from tissue donation including egg cell donation or any other tissue/blood/organ donations until at least 1 year following LD chemotherapy.
10. Male subjects must: • Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a FCBP, even if he has undergone a successful vasectomy from screening until at least 1 year following LD chemotherapy • Refrain from tissue donation including sperm or any other tissue/blood/organ donations from screening until at least 1 year following LD chemotherapy.

Exclusion criteria 25

1. Subject used any investigational agents within 14 days prior to leukapheresis.
2. Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment.
3. Inadequate pulmonary function defined as oxygen saturation (Sa02) < 92 % on room air.
4. Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed.
5. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy.
6. Subject has received ASCT within 12 weeks prior to leukapheresis.
7. Subject has history of primary immunodeficiency.
8. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C.
9. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
10. Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following noninvasive malignancies: a. Basal cell carcinoma of the skin b. Squamous cell carcinoma of the skin c. Carcinoma in situ of the cervix d. Carcinoma in situ of the breast e. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
11. Subject is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during participation in the study.
12. Subject received any of the following within the last 14 days prior to leukapheresis: a. Plasmapheresis b. Major surgery (as defined by the investigator) c. Radiation therapy other than local therapy for myeloma associated bone lesions d. Use of any systemic anti-myeloma drug therapy.
13. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab.
14. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
15. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. This includes systemic fungal, bacterial, viral, or other infection that is uncontrolled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antimicrobial treatment) or requiring IV antimicrobials for management.
16. Subject has any condition that confounds the ability to interpret data from the study.
17. Subject with known central nervous system (CNS) involvement with myeloma.
18. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.
19. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
20. Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis.
21. Subject has nonsecretory MM.
22. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) < 1,000/μL b. Platelet count < 50,000/ mm3 in the absence of transfusion support (platelet transfusion within 7 days prior to screening) c. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level) d. Serum Creatinine Clearance (CrCl) < 45 mL/min e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN) g. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome h. International ratio (INR) or partial thromboplastin time (PTT) > 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
23. Echocardiogram (ECHO) or multi-gated acquisition (MUGA) with left ventricular ejection fraction < 45%.
24. For Cohort 1b, previous treatment with any GPRC5D-targetedtherapy or T-cell engagers.
25. For Cohort 1b, known allergies, hypersensitivity, or intolerance to talquetamab or its excipients (please refer to TALVEYTM Product Information).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall response rate (ORR) (Cohort 1)
2. Complete response (CR) rate Cohort 1b,Cohort2a,Cohort 2b,Cohort 2c,and Cohort 3

Secondary endpoints 12

1. Complete response (CR) rate (Cohort 1)
2. Overall response rate (ORR) Cohort 1b, 2a, b,cand Cohort 3
3. Very good partial response (VGPR) rate (Cohort 2c)
4. Time to response (TTR)
5. Duration of response (DoR)
6. Progression-free survival (PFS)
7. Time to progression (TTP)
8. Overall survival (OS)
9. Pharmacokinetics
10. Immunogenicity
11. Health-related Quality of Life (HRQoL)
12. Feasibility of lenalidomide maintenance therapy post-bb2121 infusion (Cohort 3)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 4

Locations

3 EU/EEA countries · 4 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 39 files

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

Application history

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