A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD38 Antibody and Lenalidomide

Relapsed or Refractory Multiple Myeloma Clinical Trial

— MonumenTAL-6  

Official title:

A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pomalidomide, Bortezomib, and Dexamethasone (PVd) in Participants With Relapsed or Refractory Myeloma Who Have Received 1 to 4 Prior Lines of Therapy Including an Anti-CD38 Antibody and Lenalidomide

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06208150
• Other study ID #: 64407564MMY3009
• Secondary ID: 64407564MMY30092
• Status: Recruiting
• Phase: Phase 3
• Start date: January 22, 2024
• Est. completion date: June 30, 2030

Study information

• Verified date: June 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 compare the effectiveness of either talquetamab plus pomalidomide (Tal-P) or talquetamab plus teclistamab (Tal-Tec) with elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 795
• Est. completion date: June 30, 2030
• Est. primary completion date: April 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented multiple myeloma as defined by the criteria below: (a) multiple myeloma diagnosis according to the international myeloma working group (IMWG) diagnostic criteria (b) measurable disease at screening as assessed by central laboratory, defined by any of the following: (i) serum M-protein level greater than or equal to (>=) 0.5 gram per deciliter (g/dL); or (ii) urine M-protein level >= 200 milligram (mg) per 24 hours; or (iii) light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio

• Relapsed or refractory disease as defined below: a) Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment

• Documented evidence of PD or failure to achieve a minimal response to the last line of therapy based on investigator's determination of response by IMWG criteria on or after their last regimen

• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment

• A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6months after the last dose of study treatment

Exclusion Criteria:

• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients

• Stroke, transient ischemic attack, or seizure within 6 months prior to signing informed consent form (ICF)

• Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment

• A maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14-day period before the first dose of study drug

• Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Drug:
• Talquetamab
Talquetamab will be administered as a SC injection.
• Pomalidomide
Pomalidomide will be administered orally.
• Teclistamab
Teclistamab will be administered as a SC injection.
• Elotuzumab
Elotuzumab will be administered intravenously.
• Dexamethasone
Dexamethasone will be administered either orally or intravenously.
• Bortezomib
Bortezomib will be administered as a SC injection.

Locations

Country	Name	City	State
Argentina	Fundaleu	Buenos Aires
Argentina	Hospital Aleman	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma de Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide
Australia	Box Hill Hospital	Box Hill
Australia	St. Vincent's Hospital	Darlinghurst
Australia	St Vincents Hospital Melbourne	Fitzroy
Australia	Gold Coast University Hospital	Southport
Australia	Perth Blood Institute	West Perth
Australia	Wollongong Hospital	Wollongong
Belgium	Grand Hopital de Charleroi, site Notre Dame	Charleroi
Belgium	Ziekenhuis Oost-Limburg	Genk
Belgium	Ghent University Hospital	Gent
Belgium	AZ Nikolaas - Campus Sint-Niklaas Moerland	Sint-Niklaas
Brazil	DF Star	Brasilia
Brazil	Fundacao Universidade de Caxias do Sul	Caxias do Sul
Brazil	Hospital Erasto Gaertner- Liga Paranaense de Combate ao Cancer	Curitiba
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Recife
Brazil	Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)	Rio de Janeiro
Brazil	Hospital de Base da Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Jose do Rio Preto
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia	Sao Paulo
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont	Montreal	Quebec
Canada	University Health Network UHN Princess Margaret Cancer Centre	Toronto	Ontario
China	Beijing Chaoyang Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Peking University People s Hospital	Beijing
China	Changzhou No 2 Peoples Hospital	Changzhou
China	Nanfang Hospital of Southern Medical Hospital	Guangzhou
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	First hospital affiliated of Zhejiang Medical university	Hangzhou
China	The First Affiliated Hospital of NanChang University	Nanchang
China	Shanghai Fourth People s Hospital	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	Tongji Hospital, Tongji Medical College of HUST	Wuhan
Czechia	Fakultni nemocnice Brno	Brno - Bohunice
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	University Hospital Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava
Denmark	Aarhus University Hospital	Aarhus
Denmark	Odense University Hospital	Odense C
Denmark	Vejle Hospital	Vejle
France	Hopital Claude Huriez	Lille
France	CHU de Limoges Hopital Dupuytren	Limoges
France	Institut Paoli Calmettes	Marseille
France	CHU Nantes	Nantes
France	Hopital Saint Louis	Paris
France	CHU de Bordeaux - Hospital Haut-Leveque	Pessac Cedex
France	CHU Lyon Sud	Pierre-Benite
France	Institut de Cancerologie Strasbourg Europe ICANS	Strasbourg
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse Cedex 9
France	CHRU Tours Hopital Bretonneau	TOURS Cedex 01
Germany	Klinikum Augsburg	Augsburg
Germany	Universitaetsklinikum Halle Saale	Halle (Saale)
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Magdeburg A.oe.R	Magdeburg
Germany	Klinikum rechts der Isar der TU Muenchen	München
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Greece	251 Airforces Hospital	Athens
Greece	Alexandra General Hospital of Athens	Athens
Greece	Anticancer Hospital of Thessaloniki Theageneio	Thessaloniki
India	Fortis Memorial Research Institute	Gurgaon
India	Deenanath Mangeshkar Hospital and Research Centre	Pune
Israel	Shamir Medical Center (Assaf Harofeh)	Be'er Ya'akov
Israel	Carmel Medical Center	Haifa
Israel	Rabin Medical center - Petah-Tikva	Petah-Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv-Yafo
Italy	Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo Alessandria	Alessandria
Italy	oncologia medica - Oncology	Brindisi
Italy	ARNAS Garibaldi P O Nesima	Catania
Italy	Ospedale Policlinico San Martino IRCCS	Genova
Italy	Asst Ovest Milanese - Ospedale Di Legnano	Legnano
Italy	Fondazione IRCCS Ca Granda Ospedale Policlinico Di Milano	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Presidio Ospedaliero Pescara	Pescara
Italy	Ospedale S. Maria Delle Croci	Ravenna
Italy	Oncologia Medica-Città Della Salute E Della Scienza Di Torino	Torino
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona
Japan	Juntendo University Hospital	Bunkyo Ku
Japan	Fukuoka University Hospital	Fukuoka
Japan	Kanazawa University Hospital	Kanazawa
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto
Japan	National Hospital Organization Nagasaki Medical Center	Nagasaki
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Hyogo Medical University Hospital	Nishinomiya-shi
Japan	Japanese Red Cross Osaka Hospital	Osaka
Japan	Sapporo City General Hospital	Sapporo
Japan	Japanese Red Cross Medical Center	Shibuya-ku
Japan	Iwate Medical University Hospital	Shiwa-gun
Japan	Osaka University Hospital	Suita-City
Japan	Shizuoka Cancer Center	Sunto-gun
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tottori University Hospital	Tottori
Japan	Kanagawa Cancer Center	Yokohama City
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St Mary s Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Netherlands	Flevoziekenhuis	Almere
Netherlands	Haga ziekenhuis	Den Haag
Netherlands	Catharinaziekenhuis	Eindhoven
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Netherlands	Isala Kliniek	Zwolle
Poland	Wojewodzki Szpital Specjalistyczny	Biala Podlaska
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza	Brzozow
Poland	Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach	Kielce
Poland	Centrum Onkologii Ziemii Lubelskiej	Lublin
Poland	Uniwersytecki Szpital Kliniczny Nr 1 PUM im prof Tadeusza Sokolowskiego w Szczecinie	Szczecin
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Spain	Hosp. de Cabuenes	Asturias
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. de Burgos	Burgos
Spain	Hosp. San Pedro de Alcantara	Cáceres
Spain	Hosp. Univ. Virgen de Las Nieves	Granada
Spain	Hosp. Univ. Lucus Augusti	Lugo
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Son Espases	Palma de Mallorca
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Complejo Hosp de Navarra - Hosp de Navarra	Pamplona
Spain	Hosp Clinico Univ de Salamanca	Salamanca
Spain	Hosp. Univ. Donostia	San Sebastian
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Clinico Univ. de Santiago	Santiago de Compostela
Sweden	Skanes universitetssjukhus	Lund
Sweden	Akademiska Sjukhuset	Uppsala
Sweden	Varberg Hospital	Varberg
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Liv Hospital Ankara	Ankara
Turkey	Pamukkale University Medical Faculty	Denizli
Turkey	Medipol University Hospital	Istanbul
Turkey	Ondokuz Mayis University	Samsun
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	University Hospitals Plymouth NHS Trust	Plymouth
United Kingdom	Queen Alexandra Hospital	Portsmouth

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.	Up to 6 years 5 months
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants with best overall response of partial response (PR) or better according to international myeloma working group (IMWG) response criteria.	Up to 6 years 5 months
Secondary	Complete Response (CR) or Better Rate	CR or better is defined as the percentage of participants with best overall response of CR or better according to IMWG response criteria.	Up to 6 years 5 months
Secondary	Very Good Partial Response (VGPR) or Better Rate	VGPR or better is defined as the percentage of participants with best overall response of VGPR or better rate according to IMWG response criteria.	Up to 6 years 5 months
Secondary	Minimal Residual Disease (MRD)-negative CR Rate	MRD-negative CR is defined as the percentage of participants who achieve both CR or better and MRD negativity at a threshold of 10^-5 at any timepoint after the date of randomization and before disease progression or start of subsequent antimyeloma therapy (SST).	Up to 6 years 5 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to the date of participant's death.	Up to 6 years 5 months
Secondary	Progression Free Survival on Next-line Therapy (PFS2)	PFS2 is defined as time from randomization to progression on the next line of therapy or death, whichever comes first.	Up to 6 years 5 months
Secondary	Time to Next Treatment (TTNT)	TTNT is defined as the time from randomization to the start of SST.	Up to 6 years 5 months
Secondary	Serum Concentration of Talquetamab and Teclistamab	Serum concentration of talquetamab and teclistamab will be reported.	Up to 6 years 5 months
Secondary	Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab and Teclistamab	Number of participants with ADAs to talquetamab and teclistamab will be reported.	Up to 6 years 5 months
Secondary	Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The MySIm-Q is a disease-specific patient-reported outcome (PRO) assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30). It includes 17 items resulting in a symptom subscale and an impact subscale.	Up to 6 years 5 months
Secondary	Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. EORTC-QLQ-C30 Version 3 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 or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("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 high scale score represents a higher response level.	Up to 6 years 5 months
Secondary	Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Up to 6 years 5 months
Secondary	Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Patient Global Impression -Severity (PGI-S)	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and EORTC-QLQ-C30 in this population. The response options are presented as a 5-point verbal rating scale from "none" to "very severe."	Up to 6 years 5 months
Secondary	Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The epstein taste survey consists of 17 items from the full 71 item PRO instrument, specific to taste changes developed for use in patients with head and neck cancer as a composite of the Vanderbilt Head and Neck Symptom Survey.	Up to 6 years 5 months
Secondary	Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by MySIm-Q	Change from baseline in symptoms, functioning, and HRQoL as assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific patient-reported outcome (PRO) assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30). It includes 17 items resulting in a symptom subscale and an impact subscale.	Up to 6 years 5 months
Secondary	Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30	Change from baseline in symptoms, functioning, and HRQoL as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 Version 3 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 or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("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 high scale score represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale or item represents a high level of symptomatology or problems.	Up to 6 years 5 months
Secondary	Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EQ-5D-5L	Change from baseline in symptoms, functioning, and HRQoL as assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Up to 6 years 5 months
Secondary	Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by PGI-S	Change from baseline in symptoms, functioning, and HRQoL as assessed by PGI-S will be reported. The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and EORTC-QLQ-C30 in this population. The response options are presented as a 5-point verbal rating scale from "none" to "very severe."	Up to 6 years 5 months
Secondary	Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey	Change from baseline in symptoms, functioning, and HRQoL as assessed by epstein taste survey will be reported. The epstein taste survey consists of 17 items from the full 71 item PRO instrument, specific to taste changes. developed for use in patients with head and neck cancer as a composite of the Vanderbilt Head and Neck Symptom Survey.	Up to 6 years 5 months
Secondary	Percentage of Participants With Meaningful Improvement in HRQoL as Assessed by EORTC-QLQ-C30	Percentage of participants with meaningful improvement in HRQol as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 Version 3 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 or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("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 high scale score represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale or item represents a high level of symptomatology or problems.	Up to 6 years 5 months