| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or Refractory Multiple Myeloma |
|
| 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 | 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 |
|
| 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): To evaluate the efficacy of
teclistamab at the RP2D |
|
| E.2.2 | Secondary objectives of the trial |
•To characterize the pharmacokinetics and pharmacodynamics of JNJ-64007957
•To assess the immunogenicity of JNJ 64007957
•To evaluate the preliminary antitumor activity of JNJ 64007957 at the RP2D(s) in Part 2
Part 3:
•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 |
|
| 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 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, B,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 B: received ≥4 prior lines of therapy and whose disease is penta-drug refractory to an anti-CD38 monoclonal antibody, ≥2 PIs, ≥2 IMiDs (refractory multiple myeloma as defines by IMWG consensus criteria).
- 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 lab values meeting the predefined criteria during the Screening Phase (see table on pg 107-108 of protocol)
6. Women 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. Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (<1% / year failure rate) from the time of signing the ICF during the study and for 90 days after the last dose of study drug. Contraception must be consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials.
When a woman 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)
–A woman using hormonal contraceptives must use an additional barrier method.
For full inclusion criteria, refer to section 4.2 inclusion criteria of the protocol. |
|
| 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 to the 9th/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
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, such as:
•Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection
•Active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing
•Psychiatric conditions (eg, alcohol or drug abuse), dementia, or altered mental status
•Stroke or seizure within 6 months of signing ICF.
•Any other issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Any potential subject who meets any of the following criteria will be excluded from participating in Part 3:
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
Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or multiple-gated acquisition scan (performed ≤8 weeks prior to enrollment)
Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
•Non-muscle invasive bladder cancer.
•Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
•Noninvasive cervical cancer treated within the last 24 months that is considered completely cured.
•Localized prostate cancer (N0M0):
o With a Gleason score of 6, treated within the last 24 months or untreated and under surveillance.
o With a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence,
o Or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
•Breast cancer:
o Adequately treated lobular carcinoma in situ or ductal carcinoma in situ,
o Or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence.
•Malignancy that is considered cured with minimal risk of recurrence.
18. Live, attenuated vaccine within 4 weeks prior to the first dose of teclistamab.
For full exclusion criteria, refer to pg 117-121 of the protocol. |
|
| 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): ORR (PR or better) as defined by the IMWG criteria |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to day 21 for standard dose and up to day 28 for priming dose
2. From signing of Informed Consent Form (ICF) up to follow up (approximately up to 6 months)
3. Up to 2 years |
|
| 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:
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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| All endpoints: Up to 2 years |
|
| 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 |
|
| 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 |
|
| 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 | 7 |
| 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Spain |
| Sweden |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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