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JOURNAL ONKOLOGIE – STUDIE

A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma

Rekrutierend

NCT-Nummer:
NCT04108195

Studienbeginn:
Februar 2020

Letztes Update:
29.01.2021

Wirkstoff:
Daratumumab, Talquetamab, Teclistamab, Pomalidomide

Indikation (Clinical Trials):
Multiple Myeloma, Neoplasms, Plasma Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Janssen Research & Development, LLC

Collaborator:
-

Studienleiter

Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC

Kontakt

Studienlocations
(3 von 25)

Universitatsklinikum Freiburg
79106 Freiburg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Universitaetsklinikum Hamburg Eppendorf
20246 Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps
Universitaetsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Onkologisches Zentrum Universitätsklinikum Würzburg
Josef-Schneider-Straße 6
97080 Würzburg
DeutschlandNoch nicht rekrutierend» Google-Maps
City of Hope National Medical Center
91010 Duarte
United StatesRekrutierend» Google-Maps
University of California, San Francisco
94143 San Francisco
United StatesRekrutierend» Google-Maps
Mount Sinai Medical Center
10029 New York
United StatesRekrutierend» Google-Maps
Levine Cancer Institute
28204 Charlotte
United StatesRekrutierend» Google-Maps
Wake Forest Baptist Medical Center
27157 Winston-Salem
United StatesRekrutierend» Google-Maps
University of Pennsylvania
19104 Philadelphia
United StatesNoch nicht rekrutierend» Google-Maps
Vanderbilt - Ingram Cancer Center
37212 Nashville
United StatesRekrutierend» Google-Maps
Medical College Of Wisconsin
53226 Milwaukee
United StatesRekrutierend» Google-Maps
Tom Baker Cancer Centre
T2N 4N2 Calgary
CanadaNoch nicht rekrutierend» Google-Maps
Vancouver General Hospital
V5Z 1M9 Vancouver
CanadaZurückgezogen» Google-Maps
University Health Network (UHN) Princess Margaret Cancer Centre
M5G 2M9 Toronto
CanadaNoch nicht rekrutierend» Google-Maps
Hosp. Clinic I Provincial de Barcelona
08036 Barcelona
SpainRekrutierend» Google-Maps
Inst. Cat. Doncologia-H Duran I Reynals
08908 Barcelona
SpainRekrutierend» Google-Maps
Hosp. Clinico Univ. de Salamanca
37007 Salamanca
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Part 1: Number of Participants With Dose Limiting Toxicity (DLT) (Time Frame - Cycle 1 (Up to 28 days)):
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.

2. Part 1: Number of Participants With Dose Limiting Toxicity by Severity (Time Frame - Cycle 1 (Up to 28 days)):
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.

3. Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Time Frame - Up to 48 Weeks):
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.

4. Part 2: Number of Participants With Adverse Events and SAEs by Severity (Time Frame - Up to 48 Weeks):
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.

Secondary outcome:

1. Serum Concentration of Daratumumab (Time Frame - Up to 40 Weeks):
Serum concentration of daratumumab will be assessed.

2. Serum Concentration of Talquetamab (Time Frame - Up to 40 Weeks):
Serum concentration of talquetamab will be assessed.

3. Serum Concentration of Teclistamab (Time Frame - Up to 40 Weeks):
Serum concentration of teclistamab will be assessed.

4. Biomarker Assessment of Daratumumab (Time Frame - Up to Cycle 7 Day 1 (each cycle of 28-days)):
Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.

5. Biomarker Assessment of Talquetamab (Time Frame - Up to Cycle 7 Day 1 (each cycle of 28-days)):
Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.

6. Biomarker Assessment of Teclistamab (Time Frame - Up to Cycle 7 Day 1 (each cycle of 28-days)):
Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.

7. Number of Participants With Anti-Drug Antibodies to Daratumumab (Time Frame - Up to 40 Weeks):
Number of participants with anti-drug antibodies to daratumumab will be assessed.

8. Number of Participants With Anti-Drug Antibodies to Talquetamab (Time Frame - Up to 40 Weeks):
Number of participants with anti-drug antibodies to talquetamab will be assessed.

9. Number of Participants With Anti-Drug Antibodies to Teclistamab (Time Frame - Up to 40 Weeks):
Number of Participants with anti-drug antibodies to teclistamab will be assessed.

10. Overall Response Rate (ORR) (Time Frame - Up to 48 Weeks):
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.

11. Clinical Benefit Rate (Time Frame - Up to 48 Weeks):
Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.

12. Duration of Response (DOR) (Time Frame - Up to 48 Weeks):
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.

13. Time to Response (Time Frame - Up to 48 Weeks):
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.

Studien-Arme

  • Experimental: Part 1: Dose Escalation
    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.
  • Experimental: Part 2: Dose Expansion
    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.

Geprüfte Regime

  • Daratumumab (JNJ-54767414, Darzalex):
    Participants will receive daratumumab.
  • Talquetamab (JNJ-64407564):
    Participants will receive talquetamab.
  • Teclistamab (JNJ-64007957):
    Participants will receive teclistamab.
  • Pomalidomide:
    Participants will receive pomalidomide.

Quelle: ClinicalTrials.gov


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