Description:
The purpose of this study is to characterize the safety of Talquetamab and to determine the
recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab
(Part 1 [Dose Escalation]) and to further characterize the safety of Talquetamab at the
recommended Phase 2 dose(s) (RP2Ds) (Part 2 [Dose Expansion]).
Title
- Brief Title: Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma
- Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
CR108404
- SECONDARY ID:
2017-002400-26
- SECONDARY ID:
64407564MMY1001
- NCT ID:
NCT03399799
Conditions
- Hematological Malignancies
Interventions
| Drug | Synonyms | Arms |
|---|
| Talquetamab | | Part 1: Dose Escalation (Talquetamab) - Intravenous (IV) |
Purpose
The purpose of this study is to characterize the safety of Talquetamab and to determine the
recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab
(Part 1 [Dose Escalation]) and to further characterize the safety of Talquetamab at the
recommended Phase 2 dose(s) (RP2Ds) (Part 2 [Dose Expansion]).
Detailed Description
The study will be conducted in 2 parts: dose escalation and dose expansion. The study will
evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of
Talquetamab 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 the last study assessment
for the last participant in the study. Study record NCT04634552 is Phase 2 part of this study
and study record NCT03399799 is Phase 1 part of this study.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1: Dose Escalation (Talquetamab) - Intravenous (IV) | Experimental | Participants will receive IV infusion of Talquetamab at minimum anticipated biologic effect level (MABEL)-based starting dose until the completion of the end of treatment visit. Subsequent dose levels will be selected based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and preliminary antitumor activity data. | |
| Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC) | Experimental | Participants will receive Talquetamab SC. The dose levels will be selected to identify safe and tolerable putative RP2D(s). | |
| Part 2: Dose Expansion (Talquetamab) | Experimental | Participants will receive IV infusion or SC injection of Talquetamab at each putative recommended Phase 2 dose(s) (RP2D[s]) as determined in Part 1. | |
Eligibility Criteria
Inclusion Criteria:
- Documented initial diagnosis of multiple myeloma according to International Myeloma
Working Group (IMWG) diagnostic criteria
- Part 1: Participants with measurable multiple myeloma who have progressed on, or could
not tolerate, all available established therapies. Part 2: Participants with multiple
myeloma measurable by central laboratory assessment who have progressed on, or could
not tolerate, all available established therapies; Serum monoclonal paraprotein
(M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine
M-protein level >=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma
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 laboratory assessments are not available, relevant local laboratory
measurements must exceed the minimum required level by at least 25%
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- 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 (Beta human chorionic gonadotropin [beta-hCG]) or urine
- 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 and able 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:
- Vaccinated with live, attenuated vaccine within 4 weeks or as recommended by the
product manufacturer prior to the first dose, during treatment, or within 100 days of
the last dose of Talquetamab
- Toxicities from previous anticancer therapies should have resolved to baseline levels
or to Grade 1 or less except for alopecia or peripheral neuropathy
- Received a cumulative dose of corticosteroids equivalent to greater than or equal to (
>=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of
study drug (does not include pretreatment medication)
- An allogenic stem cell transplant within 6 months before first dose of study drug.
Participants who received an allogeneic transplant must be off all immunosuppressive
medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an
autologous stem cell transplant less than or equal to (<=) 12 weeks before first dose
of study drug
- Documented history of central nervous system (CNS) involvement or exhibits clinical
signs of meningeal involvement of multiple myeloma. If either is suspected, whole body
magnetic resonance imaging (MRI) and lumbar cytology are required
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1: Dose-limiting Toxicity (DLT) |
| Time Frame: | Up to Day 28 |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Part 1: Talquetamab Serum Concentrations |
| Time Frame: | Up to 8 weeks |
| Safety Issue: | |
| Description: | Serum concentrations will be calculated for Talquetamab. |
| Measure: | Part 1 and Part 2: Biomarker Assessment |
| Time Frame: | Up to Cycle 7 Day 1 (each cycle of 21-days) |
| Safety Issue: | |
| Description: | Serum cytokine concentrations will be measured pre- and post-infusion of Talquetamab for biomarker assessment. |
| Measure: | Part 1: Number of Participants with Talquetamab Antibodies |
| Time Frame: | Up to 8 weeks |
| Safety Issue: | |
| Description: | Antibodies to Talquetamab will be assessed to evaluate potential immunogenicity. |
| Measure: | Part 2: Overall Response Rate (ORR) |
| Time Frame: | Approximately 2.10 years |
| Safety Issue: | |
| Description: | ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria. |
| Measure: | Part 2: Clinical Benefit Rate (CBR) |
| Time Frame: | Approximately 2.10 years |
| Safety Issue: | |
| Description: | CBR is defined as the proportion of participants who have a minimal response (MR) or better according to the IMWG criteria. |
| Measure: | Part 2: Duration of Response (DOR) |
| Time Frame: | From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (approximately 2.10 years) |
| Safety Issue: | |
| Description: | DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of PD, per IMWG criteria. |
| Measure: | Part 2: Time to Response (TTR) |
| Time Frame: | From the date of first dose of study drug to the date of initial documentation of a response (approximately 2.10 years) |
| Safety Issue: | |
| Description: | TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better. |
| Measure: | Part 2: Progression-Free Survival (PFS) |
| Time Frame: | Every 16 weeks until end of study, participant dies, withdrawn consent, or lost to follow up (up to 18 months) |
| Safety Issue: | |
| Description: | PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
July 16, 2021
