Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1)

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  • 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
  • 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:

  • Prior treatment with any B cell maturation antigen (BCMA) targeted therapy
  • 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
  • Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
  • 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)
  • Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Additional Trial Information

Phase 1

Enrollment: 282 patients (estimated)

View More

Published Results

Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM)

May 28, 2021

  • As of Feb 4, 2021, 156 pts received teclistamab (IV n = 84; SC n = 72). The RP2D, identified as weekly SC 1500 µg/kg teclistamab with 60.0 and 300 µg/kg step-up doses, was given to 40 pts (median follow-up 4.3 mo [range 1.1–10.4+]).
  • Patients dosed at the RP2D (median age, 62.5 y [range, 39–84]; 65% male) had received a median of 5 prior lines of therapy (range 2–11; 100% triple-class exposed; 65% penta-drug exposed; 83% triple-class refractory; 35% penta-drug refractory; 85% refractory to their last line of therapy).
  • There were no dose-limiting toxicities at the RP2D in part 1. The most common AEs at the RP2D were CRS (70%; grade 3/4 0) and neutropenia (60%; grade 3/4 40%); grade 1 neurotoxicity was reported in 1 (3%) patient.
  • Median time to CRS onset was later with SC vs IV dosing (day after SC injection vs day of IV infusion).
  • The overall response rate in response-evaluable patients treated at the RP2D (n = 40) was 65%;
    • 58% achieved a very good partial response or better and 30% achieved a complete response (CR) or better;
    • median time to first confirmed response was 1.0 mo (range 0.2–3.1).
  • At the RP2D, median duration of response was not reached; 23 of 26 responders (88%), after median follow-up of 5.3 mo (range 1.2–10.4+), were alive and continuing on treatment with responses deepening over time.
  • Of 14 evaluable pts across all cohorts, 9 with CR were minimal residual disease–negative at 10-6. At the RP2D, teclistamab exposure was sustained across the dosing interval and exceeded target levels, and consistent T cell activation was observed.
Updated Phase 1 Results of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM)

December 02, 2020

As of 20 Jul 2020, iv teclistamab (0.3–720 µg/kg) and sc teclistamab (80–3000 µg/kg) were received by 84 and 44 pts, respectively. Overall, median age was 64 y (24–82), median number of prior lines of therapies (LOT) was 6 (2–14), 95%/79% triple-class exposed/refractory, 70%/38% penta-drug exposed/refractory, and 91% refractory to last LOT. AEs in >20% of pts (both iv and sc combined) included anemia (55%), neutropenia (55%), thrombocytopenia (41%), and leukopenia (26%), as well as non-hematologic events of CRS (53%), pyrexia (28%), diarrhea (24%), cough (23%), fatigue (23%), nausea (22%), back pain (20%), and headache (20%). 39% of pts had treatment-related grade ≥3 AEs; neutropenia (23%) and anemia (9%) were most frequent. CRS occurred in 55% and 50% of pts with iv and sc dosing, respectively, tending to occur later (relative to the most recent dose) with sc administration (median time to onset of 1.0 day iv and 2.0 days sc). CRS events were all gr 1 (n=51) or 2 (n=17) and generally confined to initial doses. 5% of pts (all iv) had neurotoxicity (2% gr ≥3), and 12% had treatment-related infusion/injection related reaction (including 4 infusion reactions [all iv, 5%] and 11 injection related reactions [all sc, 25%], all gr 1/2). Gr 3 or higher infection-related AEs were reported in 15% of pts (3% treatment related). Four gr 5 AEs were reported (all iv and considered unrelated to treatment by investigator except for 1 case of pneumonia).

120 pts were evaluable for response, with the highest and most active dose levels of 270 µg/kg and 720 µg/kg weekly for iv and 720 µg/kg and 1500 µg/kg weekly for sc (of note, response data for 3000 µg/kg sc is not yet mature). Combining these 4 iv and sc dose levels, ORR was 30/47 (63.8%, including n=24 with very good partial response [VGPR] or better and n=9 with complete response [CR] or better). 1500 µg/kg sc was selected as a RP2D, and currently at this dose, 6 of 6 pts are in response (3 PR, 1 VGPR, 2 stringent CR) with progressive deepening of responses over time.

Teclistamab Appears Safe at All Doses for Relapsed/Refractory Myeloma Treatment

May 30, 2020

  • The study involved 78 patients with relapsed/refractory myeloma who received teclistamab — a bispecific duo antibody that binds to BCMA and CD3 – intravenously.
  • Median age was 64 years old (range, 24-82), and the median number of prior therapies was 6 (range, 2-14).
  • Overall, 72% of participants were triple-class exposed, 62% triple-class refractory, and 51% penta-drug refractory.
  • Part 1 of the study was a dose-escalation trial, with a primary objective of finding the doses for part 2. Doses ranged from 0.3-720 µg/kg weekly, and there was a 67% overall response rate (ORR; 50% ≥ VGPR) at 270 µg/kg.
  • "Response rates increased with higher doses of teclistamab," Dr. Usmani said.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

Colorado

Colorado Blood Cancer Institute Sarah Cannon at Presbyterian/St. Luke's Medical Center (HealthONE)

Denver, CO

Open and Accepting

New York

Mount Sinai Hospital Tisch Cancer Institute

New York, NY

Open and Accepting

North Carolina

Levine Cancer Institute Atrium Health

Charlotte, NC

Open and Accepting

Pennsylvania

Abramson Cancer Center University of Pennsylvania

Philadelphia, PA

Open and Accepting
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