A randomized phase 3 study of Teclistamab in combination with daratumumab verses an Investigators choice of Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Velcade, Dexamethasone in Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple MyelomaTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2020-004742-11-BE
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 578
1. =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
2. Documented multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b. Measurable disease at screening as defined by any of the following:
1) Serum M-protein level =0.5 g/dL (central laboratory); or
2) Urine M-protein level =200 mg/24 hours (central laboratory); or
3) Serum immunoglobulin free light chain =10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Received 1 to 3 prior line(s) of antimyeloma therapy (Appendix 6) including a PI and lenalidomide.
a. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory (ie, have demonstrated stable disease or progressive disease by IMWG criteria during treatment or within 60 days of completion of lenalidomide-containing regimen). Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion.
4. Documented evidence of progressive disease based on investigator’s determination of response by IMWG criteria on or after their last regimen.
5. Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment (Appendix 7).
6. Have clinical laboratory values meeting the following criteria during the Screening Phase (hemogloblin =7.5 g/dL; platelets =75x10^9/L or =50x10^9/L based on plasma cell proportion; absolute neutrophil count =1.0x10^/9; AST and ALT =2.5xULN; eGFR =30 mL/min; total bilirubin =2.0xULN; serum calcium corrected for albumin =14 mg/dL)
7. A female participant of childbearing potential must have a negative highly-sensitive serum pregnancy test at screening and also a serum or urine test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study
8. A female participant must be:
a. Not of childbearing potential, or
b. Of childbearing potential at start or at any point during the study and
1) Practicing true abstinence; or
2) Practicing 2 highly-effective methods of contraception (at least one must be a highly effective method). For participants who are of childbearing potential and treated with DPd in Arm B, see Section 6.12.3 for details regarding concomitant use of estrogen-containing products and pomalidomide.
9. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment if randomized to Arm A or for 3 months after the last dose of study treatment if randomized to Arm B.
10. A male participant must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 3 months after receiving the last dose of study treatment. If a female partner is of childbearing potential, she must also be practicing a highly effective method of contraception.
11. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 3 months after receiving the last dose of study treatment.
12. Must adhere to all restrictions and requirements specified in Secti
1. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients.
2. Received any prior BCMA-directed therapy.
3. Has disease that is considered refractory to an anti-CD38 monoclonal antibody per IMWG (stable disease or progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody).
4. Received the following prior antimyeloma therapy, in the specified time frame prior to randomization:
a. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or =5 half-lives, whichever is less
b. Investigational vaccine within 4 weeks
c. Monoclonal antibody therapy within 21 days
d. Cytotoxic therapy within 21 days
e. PI therapy within 14 days
f. IMiD agent therapy within 14 days
g. Radiotherapy within 14 days or focal radiation within 7 days
h. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months.
5. Stem cell transplant:
a. An allogeneic stem cell transplant within 6 months before randomization. Participants who received an allogeneic transplant must be off all immunosuppressive medications for =42 days without signs of graft-versus-host disease before randomization.
b. An autologous stem cell transplant within 12 weeks before randomization.
6. Received a cumulative dose of corticosteroids equivalent to =140 mg of prednisone within 14 days before randomization.
7. Received a live, attenuated vaccine within 4 weeks before randomization.
8. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma.
9. Plasma cell leukemia at the time of screening, Waldenström’s macroglobulinemia, POEMS syndrome, or primary amyloid light chain amyloidosis.
10. CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
11. Stroke, transient ischemic attack, or seizure within 6 months prior to signing ICF.
12. Participant is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.
13. Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
14.
a) NYHA stage III or IV congestive heart failure
b) MI or coronary artery bypass graft =6 months prior to randomization
c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
d) Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
15.
a) Seropositive for human immunodeficiency virus
b) Hepatitis B infection
c) Active hepatitis C infection as measured by positive HCV-RNA testing
d) COPD with a FEV1 <50% of predicted normal
e) Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
16. Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
17. Major surgery within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of Tec-Dara with DPd/DVd;Secondary Objective: - To further compare the efficacy of Tec-Dara with DPd/DVd<br>- To assess the safety profile of Tec-Dara<br>- To characterize the PK of teclistamab<br>- To assess the immunogenicity of teclistamab and daratumumab<br>- To compare the patient-reported outcomes (PROs) of Tec-Dara with DPd/DVd<br>- To evaluate the efficacy of teclistamab in-high-risk molecular subgroups;Primary end point(s): PFS per IRC;Timepoint(s) of evaluation of this end point: At dosing days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Overall response (PR or better)<br>- VGPR or better<br>- CR or better<br>- MRD negativity<br>- PFS-2<br>- OS<br>- Time to next treatment<br>- Duration of Response<br><br>-Presence and severity of AEs<br>-PK parameters using population PK approach<br>-Presence of ADAs to teclistamab and daratumumab<br>-Time to worsening of symptoms<br>-Change from baseline in symptoms, functioning, and overall HRQoL<br>-PFS, depth of response, etc in participants in high-risk molecular features;Timepoint(s) of evaluation of this end point: At dosing days