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

Hematological Malignancies Clinical Trial

— MonumenTAL-1  

Official title:

A Phase 1/2, 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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04634552
• Other study ID #: CR108920
• Secondary ID: 2017-002400-26TA
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

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 of 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a post-treatment follow-up phase (until the end of study unless the participant has died, is lost to follow up or has withdrawn consent).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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria

• Part 3: Measurable disease cohort A, cohort B, cohort C, and cohort D: multiple myeloma must be measurable by central laboratory assessment

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2

• 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 and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B and Cohort D: T cell redirection therapy within 3 months

• 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)

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Talquetamab
Talquetamab will be administered SC until disease progression.

Locations

Country	Name	City	State
Belgium	UCL - Saint Luc	Brussels
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liège - Domaine Universitaire du Sart Tilman	Liège
China	Peking University Third Hospital	Beijing
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	The 1St Affiliated Hospital of Medical College Zhejiang University	Hangzhou
China	The 1St Affiliated Hospital of Medical College Zhejiang University	Hangzhou
China	First Affiliated Hospital SooChow University	Su Zhou
China	Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science	Tianjin
China	The First Affiliated Hospital of Xian Jiaotong University	XI An Shi
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an
France	CHU Henri Mondor	Creteil
France	CHU de Montpellier, Hopital Saint-Eloi	Montpellier
France	C.H.U. Hotel Dieu - France	Nantes
France	CHU de Bordeaux - Hospital Haut-Leveque	Pessac cedex
France	Centre hospitalier Lyon-Sud	Pierre Benite cedex
France	Pôle IUC Oncopole CHU	Toulouse cedex 9
Germany	Charite Campus Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Muenster	Muenster
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Japan	Kameda General Hospital	Chiba
Japan	Fukuoka University Hospital	Fukuoka
Japan	Ogaki Municipal Hospital	Gifu
Japan	Teine Keijinkai Hospital	Hokkaido
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	Dokkyo Medical University Saitama Medical Center	Koshigaya
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kurashiki Central Hospital	Kurashiki
Japan	National Hospital Organization Matsumoto Medical Center	Matsumoto
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Japanese Red Cross Osaka Hospital	Osaka
Japan	Hiroshima West Medical Center	Otake
Japan	Iwate Medical University Hospital	Shiwa-gun
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	UMCU	Utrecht
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach	Gliwice
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Inst. Cat. Doncologia-H Duran I Reynals	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Fund. Jimenez Diaz	Madrid
Spain	Hosp. Univ. Virgen de La Arrixaca	Murcia
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo de Alarcon
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Virgen Del Rocio	Sevilla
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	University of Chicago	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Tennessee Oncology	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York
United States	NYU Langone Health	New York	New York
United States	Providence Portland Medical Center	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  China,  France,  Germany,  Israel,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	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.	Up to 2 years and 10 months
Secondary	Duration of Response (DOR)	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, or death due to PD, whichever occurs first.	Up to 2 years and 10 months
Secondary	Very Good Partial Response (VGPR) or Better Rate	VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.	Up to 2 years and 10 months
Secondary	Complete Response (CR) or Better Rate	CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.	Up to 2 years and 10 months
Secondary	Stringent Complete Response (sCR) Rate	sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.	Up to 2 years and 10 months
Secondary	Time to Response (TTR)	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.	Up to 2 years and 10 months
Secondary	Progression-Free Survival (PFS)	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.	Up to 2 years and 10 months
Secondary	Overall Survival (OS)	OS is defined as the time from the date of first dose of study drug to the date of the participant's death.	Up to 2 years and 10 months
Secondary	Minimal Residual Disease (MRD) Negative Rate	MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.	Up to 2 years and 10 months
Secondary	Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	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.	Up to 2 years and 10 months
Secondary	Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	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.	Up to 2 years and 10 months
Secondary	Number of Participants with AEs by Severity	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.	Up to 2 years and 10 months
Secondary	Number of Participants with Abnormalities in Clinical Laboratory Values	Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.	Up to 2 years and 10 months
Secondary	Serum Concentration of Talquetamab	Serum samples will be analyzed to determine concentrations of talquetamab.	Up to 2 years and 10 months
Secondary	Number of Participants with Talquetamab Antibodies	Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.	Up to 2 years and 10 months
Secondary	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)	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.	Baseline up to 2 years and 10 months
Secondary	Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)	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.	Baseline up to 2 years and 10 months
Secondary	Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS)	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).	Baseline up to 2 years and 10 months
Secondary	Overall Response Rate (ORR) in Participants with High-risk Molecular Features	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.	Up to 2 years and 10 months

External Links

•   Dose Escalation Study of JNJ-64407564 in Participants With Relapsed or Refractory Multiple Myeloma