| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the efficacy of Tec-DR versus DRd |
|
| E.2.2 | Secondary objectives of the trial |
-To further compare the efficacy of Tec-DR versus DRd
-To assess the safety and tolerability of teclistamab when administered in combination with DR
-To characterize the PK of teclistamab
-To assess the immunogenicity of teclistamab
-To assess participant’s symptoms, functioning, and HRQoL with Tec-DR versus DRd using patient reported outcomes (PRO)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. ≥18 years of age
2. Have a diagnosis of multiple myeloma according to the IMWG diagnostic criteria.
3. Be newly diagnosed and not considered a candidate for high-dose chemotherapy with ASCT due to
-Ineligible due to advanced age OR
-Ineligible due to the presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT OR
-Deferral of high-dose chemotherapy with ASCT as initial treatment.
4. Measurable disease at Screening as defined by any of the following:
-Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
-Light chain multiple myeloma in whom only measurable disease is by sFLC levels: Serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio.
5. Have an ECOG performance status score of 0 to 2.
6. Have clinical laboratory values meeting the criteria during the Screening Phase:
-Hemoglobin: ≥7.5 g/dL
-Platelets: ≥70×109/L in participants in whom <50% of bone marrow nucleated cells are plasma cells and ≥50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells.
-Absolute neutrophil count: ≥1.0×109/L
-AST and ALT: ≤2.5×ULN
-Creatinine clearance: ≥30 mL/min based on Cockcroft-Gault
-Total bilirubin: ≤2.0 × ULN
-Serum calcium corrected for albumin: ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL.
7. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and a serum or urine pregnancy test within 24 hours of the
start of study treatment and must agree to further serum or urine pregnancy tests during the study and in agreement with the global PPP or local PPP/REMS program for lenalidomide.
8. A female participant must be either of the following:
a. Not of childbearing potential, or
b. Of childbearing potential and practicing at least 2 methods of reliable contraception including 1 highly effective method of contraception throughout the study, during any dose interruptions, and through 3 months after the last dose of study treatment. Contraception must begin 4 weeks prior to dosing of lenalidomide. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy.
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 a period of 3 months after receiving the last dose of study treatment.
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 3 months after receiving the last dose of study treatment. If the male participant’s partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception. A male participant who is vasectomized must still use a condom (with or without spermicide), but the partner is not required to use
contraception.
11. A male participant must agree not to donate sperm for the purposes of reproduction during the study and for 3 months after receiving the last dose of study treatment.
12. A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study
treatment.
13. A male participant must agree not to plan to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
14. Must sign an ICF (or their legally acceptable representative must sign in accordance with local legislation) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
15. Be willing and able to adhere to the lifestyle restrictions specified in this protocol.
For a full list of inclusion criteria, please refer to section 5.1 of the study protocol. |
|
| E.4 | Principal exclusion criteria |
1. Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light chain amyloidosis.
2. Received a cumulative dose of systemic corticosteroids equivalent to ≥20 mg of dexamethasone within 14 days before randomization.
3. Received focal radiation therapy within 14 days of randomization.
4. Had plasmapheresis within 28 days of randomization.
5. Had a stroke, transient ischemic attack, or seizure within 6 months prior to randomization.
6. Has clinical signs of meningeal involvement of multiple myeloma.
7. Has COPD with an FEV1 <50% of predicted. (FEV1 testing is required for participants suspected of having COPD).
8. Has moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification.
9. Seropositive for hepatitis B: defined by a positive test HBsAg.
10. Has active hepatitis C infection as measured by positive HCV-RNA testing.
11. Participants who are human immunodeficiency virus-positive with 1 or more of the following:
a. History of AIDS-defining conditions
b. CD4 count <350 cells/mm3
c. Detectable viral load (ie, >50 copies/mL) during screening or within 6 months prior to randomization
d. Not receiving highly active antiretroviral therapy
e. Had a change in antiretroviral therapy within 6 months prior to randomization
f. Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Medical Monitor.
12. Myelodysplastic syndrome or active malignancies other than multiple myeloma.
13. Participant has 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.
14. Presence of the following cardiac conditions:
-New York Heart Association stage III or IV congestive heart failure
-Myocardial infarction or coronary artery bypass graft ≤6 months prior to randomization
-History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
-Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
15. Participant had significant traumatic injury or 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 time the participant is expected to be treated in the study.
16. Known allergies, hypersensitivity, or intolerance to teclistamab excipients.
17. Known contraindications to the use of daratumumab or lenalidomide per local prescribing information.
18. Taken any disallowed therapies before the planned first dose of study treatment.
19. Received live or live-attenuated vaccine(s) within 4 weeks prior to screening or plans to receive such vaccines during the study.
20. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
For a full list of exclusion criteria, please refer to section 5.2 of the study protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
-PFS
-Sustained MRD-negative CR (duration ≥12 months) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
-Efficacy: VGPR or better; CR or better; MRD-negative CR; PFS2; OS
-Safety: Incidence and severity of AEs, laboratory results,
and other safety parameters.
-PK: PK parameters using population PK approach
-Immunogenicity: Presence of ADAs to teclistamab
-PRO: Change from baseline in symptoms, functioning,
and HRQoL; Time to sustained worsening in symptoms, functioning, and overall HRQoL. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| Canada |
| China |
| India |
| Japan |
| Korea, Republic of |
| United States |
| Turkey |
| Austria |
| Belgium |
| Czechia |
| Denmark |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Netherlands |
| Norway |
| Poland |
| Portugal |
| Spain |
| Sweden |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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