Description:
The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) for each treatment
combination (between daratumumab plus talquetamab and teclistamab plus daratumumab with or
without pomalidomide) and to characterize the safety of each RP2D for selected treatment
combinations.
Title
- Brief Title: A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma
- Official Title: A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
CR108620
- SECONDARY ID:
2019-000330-19
- SECONDARY ID:
64407564MMY1002
- NCT ID:
NCT04108195
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Daratumumab | JNJ-54767414, Darzalex | Part 1: Dose Escalation |
| Talquetamab | JNJ-64407564 | Part 1: Dose Escalation |
| Teclistamab | JNJ-64007957 | Part 1: Dose Escalation |
| Pomalidomide | | Part 1: Dose Escalation |
Purpose
The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) for each treatment
combination (between daratumumab plus talquetamab and teclistamab plus daratumumab with or
without pomalidomide) and to characterize the safety of each RP2D for selected treatment
combinations.
Detailed Description
Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions,
increased susceptibility to infections, hypercalcemia, and renal failure. Overall rationale
of study is that daratumumab in combination with talquetamab or teclistamab may lead to
enhanced clinical responses in treatment of relapsed or refractory multiple myeloma through
multiple mechanisms of action. Daratumumab is human immunoglobulin G1 kappa monoclonal
antibody (IgG1k) that binds with high affinity to a unique epitope on cluster of
differentiation 38 (CD38) in a variety of hematological malignancies including multiple
myeloma. Talquetamab and teclistamab are bispecific T cell redirection antibodies.
Talquetamab binds to cluster of differentiation 3 (CD3) receptor complex on T cells and to G
protein-coupled receptor family C group 5-member D (GPRC5D), a 7-transmembrane receptor
protein on plasma cells and teclistamab binds to human and cynomolgus-CD3 and B cell
maturation antigen (BCMA). Purpose of study is to evaluate safety of daratumumab in
combination with talquetamab and teclistamab, and to evaluate preliminary antitumor activity
of each combination. Study consists of a screening period, treatment period (Part 1: dose
escalation and Part 2: dose expansion) and a post treatment follow-up period (after end of
treatment and up to 16 weeks after last dose. End of study is defined as last study
assessment for last participant in study. Total duration of study is approximately 2.4 years.
Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at
specified time points. Participants safety will be monitored throughout study by Study
Evaluation Team (SET). SET consists of members of sponsor's study team and participating
investigators.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1: Dose Escalation | Experimental | Participants will be assigned to either a combination of 1) daratumumab plus teclistamab or 2) daratumumab plus talquetamab or 3) daratumumab plus talquetamab plus pomalidomide or 4) daratumumab plus teclistamab plus pomalidomide. | - Daratumumab
- Talquetamab
- Teclistamab
- Pomalidomide
|
| Part 2: Dose Expansion | Experimental | Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1 until disease progression, unacceptable toxicity, withdrawal of consent, otherwise deemed necessary by the investigator or the sponsor, or end of study. | - Daratumumab
- Talquetamab
- Teclistamab
- Pomalidomide
|
Eligibility Criteria
Inclusion Criteria:
- Documented initial diagnosis of multiple myeloma according to International Myeloma
Working Group (IMWG) diagnostic criteria
- Must have either of the following: a) received at least 3 prior lines of therapy
including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2
months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of
treatment) in any order during the treatment or b) disease that is double refractory
to a PI and an IMiD
- Measurable disease at screening as defined by any of the following: Serum monoclonal
protein (M-protein) level >= 1.0 grams per deciliter (g/dL) (in non- immunoglobulin G
(IgG) myeloma, an M-protein level >=0.5 g/dL); or Urine M-protein level >=200
milligram (mg)/24 hours; or Light chain multiple myeloma: Serum immunoglobulin (Ig)
free light chain (FLC) >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig
kappa lambda FLC ratio
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at
screening and at Cycle 1, Day 1 predose
- Women of childbearing potential must have a negative highly-sensitive serum beta-human
chorionic gonadotropin (beta-hCG) pregnancy test (less than [<] 5 international units
per milliliter [IU/mL]) at screening and a negative urine or serum pregnancy test
within 24 hours before the first dose of study drug
Exclusion Criteria:
- Treatment in the prior 3 months with an anti- cluster of differentiation 38 (CD38)
therapy (example, daratumumab), or discontinuation of a prior anti-CD38 therapy at any
time due to an adverse event related to the anti-CD38 therapy
- Live, attenuated vaccine within 4 weeks prior to the first dose of study drug unless
approved by sponsor
- Active Central nervous system involvement or exhibits clinical signs of meningeal
involvement of multiple myeloma. If either is suspected, brain magnetic resonance
imaging (MRI) and lumbar cytology are required
- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Participants with resolved infection must be screened using
real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV)
deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
- Active hepatitis C infection as measured by positive hepatitis C virus- ribonucleotide
(HCV)-RNA testing. Participants with a history of Hepatitis C virus antibody
positivity must undergo HCV-RNA testing
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1: Number of Participants With Dose Limiting Toxicity (DLT) |
| Time Frame: | Cycle 1 (Up to 28 days) |
| Safety Issue: | |
| Description: | The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher. |
Secondary Outcome Measures
| Measure: | Serum Concentration of Daratumumab |
| Time Frame: | Up to 40 Weeks |
| Safety Issue: | |
| Description: | Serum concentration of daratumumab will be assessed. |
| Measure: | Serum Concentration of Talquetamab |
| Time Frame: | Up to 40 Weeks |
| Safety Issue: | |
| Description: | Serum concentration of talquetamab will be assessed. |
| Measure: | Serum Concentration of Teclistamab |
| Time Frame: | Up to 40 Weeks |
| Safety Issue: | |
| Description: | Serum concentration of teclistamab will be assessed. |
| Measure: | Biomarker Assessment of Daratumumab |
| Time Frame: | Up to Cycle 7 Day 1 (each cycle of 28-days) |
| Safety Issue: | |
| Description: | Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment. |
| Measure: | Biomarker Assessment of Talquetamab |
| Time Frame: | Up to Cycle 7 Day 1 (each cycle of 28-days) |
| Safety Issue: | |
| Description: | Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment. |
| Measure: | Biomarker Assessment of Teclistamab |
| Time Frame: | Up to Cycle 7 Day 1 (each cycle of 28-days) |
| Safety Issue: | |
| Description: | Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment. |
| Measure: | Number of Participants With Anti-Drug Antibodies to Daratumumab |
| Time Frame: | Up to 40 Weeks |
| Safety Issue: | |
| Description: | Number of participants with anti-drug antibodies to daratumumab will be assessed. |
| Measure: | Number of Participants With Anti-Drug Antibodies to Talquetamab |
| Time Frame: | Up to 40 Weeks |
| Safety Issue: | |
| Description: | Number of participants with anti-drug antibodies to talquetamab will be assessed. |
| Measure: | Number of Participants With Anti-Drug Antibodies to Teclistamab |
| Time Frame: | Up to 40 Weeks |
| Safety Issue: | |
| Description: | Number of Participants with anti-drug antibodies to teclistamab will be assessed. |
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | Up to 48 Weeks |
| Safety Issue: | |
| Description: | ORR is defined as the percentage of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria. |
| Measure: | Clinical Benefit Rate |
| Time Frame: | Up to 48 Weeks |
| Safety Issue: | |
| Description: | Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria. |
| Measure: | Duration of Response (DOR) |
| Time Frame: | Up to 48 Weeks |
| Safety Issue: | |
| Description: | DOR is defined as the time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria. |
| Measure: | Time to Response |
| Time Frame: | Up to 48 Weeks |
| Safety Issue: | |
| Description: | Time to response 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. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 11, 2021
