E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Multiple Myeloma |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10005330 |
E.1.2 | Term | Blood and lymphatic system disorders congenital |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Part 1 (Dose Escalation): To identify the recommended Phase 2 dose(s) and schedule assessed to be safe for JNJ-64007957 •Part 2 (Dose Expansion): To characterize the safety and tolerability of JNJ-64007957 at the recommended Phase 2 dose(s) (RP2Ds) •Part 3 (Phase 2) for Cohorts A and C: To evaluate the efficacy of teclistamab at the RP2D |
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E.2.2 | Secondary objectives of the trial |
•To characterize the pharmacokinetics and pharmacodynamics of teclistamab •To evaluate the preliminary antitumor activity of JNJ-64007957 at the RP2D(s) in Part 2 Part 3 for Cohorts A and C: •To further assess the efficacy of teclistamab at the RP2D •To evaluate MRD at the RP2D •To further assess the safety and tolerability of teclistamab at the RP2D |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 years of age. 2. Documented diagnosis of MM according to IMWG diagnostic criteria. 3. Part 1 and Part 2 Measurable MM that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory MM or be intolerant of those established MM therapies, and a candidate for teclistamab treatment in the opinion of the treating physician. Prior lines of therapy must include a PI, an IMiD and an anti-CD38 monoclonal antibody in any order during the course of treatment. Subjects who could not tolerate a PI, IMiD, or an anti-CD38 monoclonal antibody are allowed. In Part 2 (dose expansion), in addition to above criteria, MM must be measurable per current IMWG published guidelines by central lab assessment. If central lab assessment is not available, relevant local lab measurement must exceed the minimum required level by at least 25%. Part 3 Measurable disease Cohort A and Cohort C: MM must be measurable by central lab assessment: - Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or - Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. If central lab assessments are not available, relevant local lab measurements must exceed the min required level by at least 25%. Prior treatment: - Cohort A: Subjects must have 1) received ≥3 prior lines of therapy and 2) previously received a PI, an IMiD, and an anti-CD38 monoclonal antibody. - Cohort C: received ≥3 prior lines of therapy that included a PI, an IMiD, an anti-CD38 monoclonal antibody, and an anti-BCMA treatment (with CAR-T cells or an ADC). 4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 5. Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase (refer to clinical protocol) 6. A female subject of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (β human chorionic gonadotropin [β-hCG]) or urine. 7. Female subjects of childbearing potential and fertile male subjects who are sexually active must agree to use a highly effective method of contraception (<1% / year failure rate). Contraception must begin from the time of signing the ICF, continue during study treatment, including dose interruptions, and through 6 months and 3 months after the last dose of study drug, for female and male subjects, respectively. Contraception must be consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. When a female subject is of childbearing potential the following are required: • Subject must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly). Examples of highly effective contraceptives include: – user-independent methods: 1) implantable progestogen-only hormone contraception associated with inhibition of ovulation; 2) intrauterine device; intrauterine hormone-releasing system; 3) vasectomized partner; – user-dependent methods: 1) combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral orintravaginal or transdermal; 2) progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable)
In addition to the highly effective method of contraception, a fertile male subject: - Who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception -Who is sexually active with a woman who is pregnant must use a condom -Female and male subjects must agree not to donate eggs (ova, oocytes) or sperm, during the study and for 6 months and 3 months, respectively, after the last dose of study drug.
For full inclusion criteria, refer to section 4.1 inclusion criteria of the protocol. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with any BCMA-targeted therapy, with the exception of Cohort C in Part 3. 2. Prior antitumor therapy as follows, before the first dose of study drug: -Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. -Monoclonal antibody treatment for multiple myeloma within 21 days -Cytotoxic therapy within 21 days -Proteasome inhibitor therapy within 14 days -Immunomodulatory agent therapy within 7 days -Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months -Radiotherapy within 14 days or focal radiation within 7 days. 3. Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy. 4. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug. (does not include pretreatment medication) 5. Stem cell transplantation: -An allogeneic stem cell transplant within 6 months. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. -Received an autologous stem cell transplant ≤12 weeks before the first dose of study drug. 6. Known active CNS involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. 7. Plasma cell leukemia (>2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis. 8. Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome. 9.Hepatitis B infection or at risk for hepatitis B virus (HBV) reactivation as defined according to the American Society of Clinical Oncology guidelines 10. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation. 11. Known allergies, hypersensitivity, or intolerance to the study drug (teclistamab) or its excipients. 12. Any serious underlying medical condition. 13. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after receiving the last dose of study drug. 14. Plans to father a child while enrolled in this study or within 3 months after receiving the last dose of study drug. 15. Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration. 16. The following cardiac conditions: - New York Heart Association stage III or IV congestive heart failure -Myocardial infarction or coronary artery bypass graft (CABG) ≤6 months prior to enrollment -History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration -History of severe non-ischemic cardiomyopathy 17. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. 18. Live, attenuated vaccine within 4 weeks prior to the first dose of teclistamab. Non-live or non-replicating vaccines authorized for emergency use (eg., COVID-19) are allowed.
For full exclusion criteria, refer to Section 4.2 exclusion criteria of the clinical protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Part 1 (Dose Escalation): Frequency and type of dose-limiting toxicity (DLT) •Part 2 (Dose Expansion): Occurrence and severity of adverse events, serious adverse events, and laboratory values •Part 3 (Phase 2) for Cohorts A and C: ORR (PR or better) as defined by the IMWG criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to the clinical protocol for the Schedule of Activities and associated Tables |
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E.5.2 | Secondary end point(s) |
•Parts 1 & 2 1. Pharmacokinetic parameters and pharmacodynamic markers including but not limited to depletion of BCMA expressing cells, systemic cytokine concentrations, and markers of T cell activation 2. Assess response rate including ORR as defined by IMWG response criteria 3. progression-free survival (PFS) 4. overall survival (OS) •Part 3 (phase 2) for Cohorts A and C: 1. DOR 2. Assess additional response parameters as defined by IMWG response criteria 3. PFS 4. OS 5. MRD-negative status 6. Occurence and severity of adverse events, serious adverse events, and laboratory values |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to the clinical protocol for the Schedule of Activities and associated Tables |
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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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
-Immunogenicity -Biomarker -Immunoregulatory activity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Dose escalation (Part 1) and expansion (Part 2) and (Part 3) Phase 2 dose expansion |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Canada |
China |
United Kingdom |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | No |
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
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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 | 2 |
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 | 2 |