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JOURNAL ONKOLOGIE – STUDIE

A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

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NCT-Nummer:
NCT04634552

Studienbeginn:
Januar 2021

Letztes Update:
31.12.2020

Wirkstoff:
Talquetamab

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Janssen Research & Development, LLC

Collaborator:
-

Studienleiter

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

Kontakt

Studienlocations (3 von 71)

Universitatsklinikum Freiburg
79106 Freiburg
(Baden-Württemberg)
Germany» Google-Maps
Universitaetsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
Germany» Google-Maps
Universitaetsklinikum Muenster
48149 Muenster
(Nordrhein-Westfalen)
Germany» Google-Maps
Klinikum Großhadern der Ludwig-Maximilians-Universität
81377 München
(Bayern)
Germany» Google-Maps
Onkologisches Zentrum Universitätsklinikum Würzburg
Josef-Schneider-Straße 6
97080 Würzburg
Deutschland» Google-Maps
University of Alabama Birmingham
35294 Birmingham
United States» Google-Maps
The University of Arizona Cancer Center
85719 Tucson
United States» Google-Maps
University of Arkansas for Medical Sciences
72205 Little Rock
United States» Google-Maps
Yale University School Of Medicine
06510 New Haven
United States» Google-Maps
Emory University - Winship Cancer Institute
30322 Atlanta
United States» Google-Maps
Center for Cancer and Blood Disorders
20817 Bethesda
United States» Google-Maps
University of Michigan Health System
48109 Ann Arbor
United States» Google-Maps
Washington University School of Medicine
63110 Saint Louis
United States» Google-Maps
University of Rochester Medical Center
14642 Rochester
United States» Google-Maps
The Ohio State University Wexner Medical Center - James Cancer Hospital
43210 Columbus
United States» Google-Maps
Providence Portland Medical Center
97213 Portland
United States» Google-Maps
University of Texas, MD Anderson Cancer Center
77030 Houston
United States» Google-Maps
University of Wisconsin Carbone Cancer Center
53792 Madison
United States» Google-Maps
CHU de Liège - Domaine Universitaire du Sart Tilman
4000 Liège
Belgium» Google-Maps
CHU de Montpellier, Hopital Saint-Eloi
34295 Montpellier
France» Google-Maps
CHU de Bordeaux - Hôpital Haut-Lévêque
33604 Pessac cedex
France» Google-Maps
Chonnam National University Hwasun Hospital
58128 Hwasun Gun
Korea, Republic of» Google-Maps
Severance Hospital, Yonsei University Health System
03722 Seoul
Korea, Republic of» Google-Maps
The Catholic University of Korea Seoul St. Mary's Hospital
06591 Seoul
Korea, Republic of» Google-Maps
Seoul National University Hospital
3080 Seoul
Korea, Republic of» Google-Maps
Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach
44102 Gliwice
Poland» Google-Maps
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
60-569 Poznan
Poland» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
02-781 Warszawa
Poland» Google-Maps
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
50-367 Wroclaw
Poland» 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. Talquetamab is a

humanized immunoglobulin G4 proline, alanine, alanine (IgG4PAA) bispecific antibody designed

to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule

found on T lymphocytes (T cell). This study consists 3 periods: screening phase (up to 28

days), treatment phase (start of study drug administration and continues until the completion

of the end of treatment [EOT (30 days (+ 7 days)] visit); and a post-treatment follow-up

phase (until the end of study unless the participant has died, is lost to follow up or has

withdrawn consent). Total duration of study is up to 2 years (after the last participant

receives their first dose). Safety, pharmacokinetics (PK), laboratory tests, and

questionnaire will be assessed at specified time points during this study. Participants

safety and study conduct will be monitored throughout the study. The corresponding study

(NCT03399799) is the Phase 1 part of the study and TALMMY1001- Part 3 is the Phase 2 part of

the study.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Documented initial diagnosis of multiple myeloma according to international myeloma

working group (IMWG) diagnostic criteria

- Part 3: Measurable disease cohort A and cohort B: multiple myeloma must be measurable

by central laboratory assessment

- 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 [hCG]) or urine

- Willing and able to adhere to the prohibitions and restrictions specified in this

protocol

Exclusion Criteria:

- Part 3 only: Cohort A only: exposed to a CAR-T or T cell redirection therapy at any

time. Cohort B: T cell redirection therapy within 3 months

- 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 >= 140 milligram (mg) of

prednisone within the 14-day period before the first dose of study drug (does not

include pretreatment medication)

- Stroke or seizure within 6 months prior to signing the informed consent form (ICF)

Studien-Rationale

Primary outcome:

1. Overall Response Rate (ORR) (Time Frame - Up to 15 months):
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.



Secondary outcome:

1. Duration of Response (DOR) (Time Frame - Up to 2 years and 10 months):
DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria.

2. Very Good Partial Response (VGPR) or Better Rate (Time Frame - Up to 2 years and 10 months):
VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.

3. Complete Response (CR) or Better Rate (Time Frame - Up to 2 years and 10 months):
CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.

4. Stringent Complete Response (sCR) Rate (Time Frame - Up to 2 years and 10 months):
sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.

5. Time to Response (TTR) (Time Frame - Up to 2 years and 10 months):
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.

6. Progression-Free Survival (PFS) (Time Frame - Up to 2 years and 10 months):
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.

7. Overall Survival (OS) (Time Frame - Up to 2 years and 10 months):
OS is defined as the time from the date of first dose of study drug to the date of the participant's death.

8. Minimal Residual Disease (MRD) Negative Rate (Time Frame - Up to 2 years and 10 months):
MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on (intent to treat) ITT similar to the other response data.

9. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Time Frame - Up to 2 years and 10 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.

10. Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability (Time Frame - Up to 2 years and 10 months):
An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.

11. Number of Participants with AEs by Severity (Time Frame - Up to 2 years and 10 months):
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.

12. Number of Participants with Abnormalities in Clinical Laboratory Values (Time Frame - Up to 2 years and 10 months):
Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.

13. Serum Concentration of Talquetamab (Time Frame - Up to 2 years and 10 months):
Serum samples will be analyzed to determine concentrations of talquetamab.

14. Number of Participants with Talquetamab Antibodies (Time Frame - Up to 2 years and 10 months):
Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.

15. Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) (Time Frame - Baseline up to 2 years and 10 months):
The EORTC- QLQ-Core-30 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week ("past week") and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

16. Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) (Time Frame - Baseline up to 2 years and 10 months):
The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.

17. Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) (Time Frame - Baseline up to 2 years and 10 months):
The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).

18. Overall Response Rate (ORR) in Participants with High-risk Molecular Features (Time Frame - Up to 2 years and 10 months):
ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups or other high-risk molecular subtypes.

Studien-Arme

  • Experimental: Part 3: Cohort A (Talquetamab)
    Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.
  • Experimental: Part 3: Cohort B (Talquetamab)
    Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

Geprüfte Regime

  • Talquetamab (JNJ-64407564):
    Talquetamab will be administered SC until disease progression.

Quelle: ClinicalTrials.gov


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