MajesTEC-1: Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma
Study Details
Study Description
Brief Summary
The purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for Teclistamab and to characterize the safety and tolerability of Teclistamab at the RP2Ds.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The study will be conducted in 2 parts, separately for IV and SC administration: dose escalation (Part 1) and dose expansion (Part 2). It will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of Teclistamab administered to adult participants with relapsed or refractory multiple myeloma. The overall safety of the study drug will be assessed by physical examinations, Eastern Cooperative Oncology Group performance status, laboratory tests, vital signs, electrocardiograms, adverse event monitoring, and concomitant medication usage. Disease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days) and to confirm stringent complete response (sCR), complete response (CR), or relapse from CR. The end of study (study completion) is defined as 2 years after the last participant in Part 3 has received his or her initial dose of teclistamab. Study record NCT04557098 is Phase 2 part of this study and study record NCT03145181 is Phase 1 part of this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Dose Escalation (IV) Participants will receive Teclistamab intravenously (IV). |
Drug: Teclistamab (IV)
Participants will receive IV infusion of Teclistamab.
Other Names:
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| Experimental: Part 2: Dose Expansion (IV) Participants will receive Teclistamab IV. |
Drug: Teclistamab (IV)
Participants will receive IV infusion of Teclistamab.
Other Names:
|
| Experimental: Part 1: Dose Escalation (SC) Participants will receive Teclistamab subcutaneously (SC). |
Drug: Teclistamab(SC)
Participants will receive SC injection of Teclistamab.
Other Names:
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| Experimental: Part 2: Dose Expansion (SC) Participants will receive Teclistamab SC. |
Drug: Teclistamab(SC)
Participants will receive SC injection of Teclistamab.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicity (DLT) [Up to Day 28]
The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
- Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [Up to 7 years and 3 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Secondary Outcome Measures
- Teclistamab Serum Concentrations [Up to 8 weeks]
Concentration assessment will be done to evaluate the effect of Teclistamab.
- Number of Participants with Teclistamab Antibodies [Up to 8 weeks]
Antibodies to Teclistamab will be assessed to evaluate potential immunogenicity.
- Preliminary Antitumor Activity of Teclistamab at the RP2D(s) in Part 2 [Up to End of Treatment (Approximately 91 days)]
Preliminary antitumor activity of Teclistamab will be done using the International Myeloma Working Group (IMWG) response criteria.
- Biomarker Assessment [Up to 8 weeks]
Biomarker assessment may be done to evaluate the effect of Teclistamab.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
-
Measurable multiple myeloma that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory multiple myeloma or be intolerant of those established multiple myeloma therapies, and a candidate for Teclistamab treatment in the opinion of the treating physician. Prior lines of therapy must include a proteasome inhibitor, an immunomodulatory drug and anti-CD38 monoclonal antibody in any order during the course of treatment. Participants who could not tolerate a proteasome inhibitor or immunomodulatory drugs and an anti-CD38 monoclonal antibody are allowed
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Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
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Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (less than [<] 1%/year failure rate) 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 participants participating in clinical trials. When a woman is of childbearing potential the following are required: A woman using hormonal contraceptives must use an additional barrier method (failure rate of <1% per year when used consistently and correctly). Examples of highly effective contraceptives for women include user-independent methods (for example, implantable progestogen-only hormone contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized partner) and user-dependent methods (for example: combined [estrogen- and progestogen-containing] hormonal contraception associated with inhibition of ovulation [oral/intravaginal/ transdermal]; progestogen-only hormone contraception associated with inhibition of ovulation [oral/injectable]. In addition to the highly effective method of contraception, a man who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (for example a condom with spermicidal foam/gel/film/cream/suppository). Additionally, a man who is sexually active with a woman who is pregnant must use a condom. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study and for 90 days after the last dose of study drug
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Participants must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease
Exclusion Criteria:
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Prior treatment with any B cell maturation antigen (BCMA) targeted therapy
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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 (example, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months; Radiotherapy within 14 days or focal radiation within & days
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Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
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Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
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Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
| 3 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215-5418 |
| 4 | Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects | New York | New York | United States | 10029 |
| 5 | Levine Cancer Institute | Charlotte | North Carolina | United States | 28204 |
| 6 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | Centre hospitalier Lyon-Sud | Pierre Benite cedex | France | 69495 | |
| 8 | CHRU Tours Hôpital Bretonneau | Tours | France | 37044 | |
| 9 | VU Medisch Centrum | Amsterdam | Netherlands | 1081 HV | |
| 10 | Hosp. Univ. Germans Trias I Pujol | Badalona | Spain | 08916 | |
| 11 | Hosp. Clinic I Provincial de Barcelona | Barcelona | Spain | 08036 | |
| 12 | Clinica Univ. de Navarra | Pamplona | Spain | 31008 | |
| 13 | Hosp. Clinico Univ. de Salamanca | Salamanca | Spain | 37007 | |
| 14 | Haematology Centre, R 51 | Stockholm | Sweden | SE-141 86 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CR108206
- 2016-002122-36
- 64007957MMY1001