| 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 |
| The Primary Objective is to compare the efficacy of teclistamab with PVd/Kd. |
|
| E.2.2 | Secondary objectives of the trial |
The Secondary Objectives are:
- To further compare the efficacy of teclistamab with PVd/Kd
- To assess the safety profile of teclistamab
- To characterize the PK of teclistamab
- To assess the immunogenicity of teclistamab
- To assess participant’s symptoms, functioning, and HRQoL with teclistamab versus PVd/Kd
- To evaluate the efficacy of teclistamab in high-risk molecular subgroups |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
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 diagnosis of multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to IMWG diagnostic criteria.
b. Measurable disease at screening as defined by any of the following:
- Serum M-protein level ≥0.5 g/dL (central laboratory); or
- Urine M-protein level ≥200 mg/24 hours (central laboratory); or
- Serum immunoglobulin free light chain ≥10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Relapsed or refractory disease as defined in the protocol:
4. Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti-CD38 monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line.
5. Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator’s determination of response by IMWG criteria.
6. Have an ECOG performance status score of 0 to 2.
7. Clinical laboratory values meeting the criteria as defined in the protocol during the Screening Phase and within 3 calendar days prior to the first dose
8. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test within 10 to 14 days prior to C1D1 and again either serum or urine pregnancy test within 24 hours to the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
9. A female participant must be either of the following:
a. Not of childbearing potential, or
b. Of childbearing potential and practicing at least 2 effective methods of contraception simultaneously, including 1 highly effective method of contraception (details in the protocol). Contraception must begin 4 weeks prior to dosing, continue during study treatment, including during dose interruptions, and through 6 months after the last dose of study treatment.
10. 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 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anticancer treatments may impair fertility.
11. 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 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.
12. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a period of 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility.
13. A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.
14. 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.
15. Must be willing and able to adhere to the lifestyle restrictions specified in protocol.
Please refer to the protocol for full inclusion criteria. |
|
| E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Received any prior BCMA-directed therapy
2. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator’s Brochure and appropriate prescribing information). Additional exclusion criteria pertaining to specific study drugs include:
a. A participant is not eligible to receive PVd as control therapy if any of the following are present:
- Received prior pomalidomide therapy.
- Does not meet criteria for bortezomib retreatment (failure to achieve at least PR to prior bortezomib treatment, or progression by IMWG criteria on therapy or within 6 months after cessation of prior bortezomib treatment).
- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib (intolerance defined as prior therapy discontinued due to any AE related to pomalidomide or bortezomib).
- Grade 1 peripheral neuropathy with pain or Grade ≥2 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
- Received a strong CYP3A4 inducer within 5 half-lives prior to randomization.
b. A participant is not eligible to receive Kd as control therapy if any of the following are present:
- Received prior carfilzomib therapy.
- Uncontrolled hypertension, defined as an average systolic blood pressure >159 mmHg or diastolic blood pressure >99 mmHg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology 2018 guidelines (Williams 2018).
- Grade 2 peripheral neuropathy with pain or Grade ≥3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any AE related to carfilzomib).
3. Participants will be excluded if intolerant to dexamethasone.
4. Received the following prior antimyeloma therapy, within the specified time frame prior to randomization as specified in protocol.
5. Live, attenuated vaccine within 4 weeks of randomization or if participant plans to receive such vaccines during the study. Vaccines approved or authorized for emergency use and non-live vaccines (eg, influenza) are allowed.
6. CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
7. Plasma cell leukemia at the time of screening, Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis.
8. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. For exceptions see protocol.
9. Stroke, transient ischemic attack, or seizure within 6 months prior to randomization.
10. Presence of the following cardiac conditions.
a. Unstable angina or New York Heart Association class III or IV congestive heart failure (Appendix 11)
b. Myocardial infarction 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
e. TTE or MUGA scan showing left ventricular ejection fraction <40%.
11. Participant had major surgery or had significant traumatic injury within 2 weeks prior to randomization, 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.
13. Seropositive for hepatitis B: defined by a positive test for HbsAg.
14. Active hepatitis C infection as measured by positive HCV-RNA testing.
15. 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 during screening or within 6 months prior to screening
d. Not receiving highly active antiretroviral therapy
e. Had a change in antiretroviral therapy within 6 months of the start of screening
f. Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the sponsor.
16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Please refer to the protocol for full exclusion criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-Free Survival (PFS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Overall response (PR or better)
2. VGPR or better
3. CR or better
4. MRD negativity
5. Duration of response
6. Time to next treatment
7. PFS2
8. OS
8. Incidence and severity of AEs, serious AEs, and laboratory results
10. PK parameters using population approach
11. Presence of ADAs to teclistamab
12. Change from baseline in symptoms, functioning, and overall HRQoL
13. Time to worsening in symptoms, functioning, and overall HRQoL
14. PFS, depth of response, etc in participants in high-risk molecular features |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 8, 10 to 13. Throughout the study
9. Predose and at timepoints as specified in the protocol |
|
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunogenicity and Patient-reported Outcomes |
|
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 74 |
| 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 |
| Israel |
| Japan |
| Malaysia |
| United States |
| Austria |
| France |
| Poland |
| Sweden |
| Netherlands |
| Spain |
| Czechia |
| Germany |
| Greece |
| Italy |
| Belgium |
| Denmark |
| Portugal |
| Turkey |
| 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
|
| Final Overall Survival analysis |
|
| 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 | |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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