A Study to Learn About the Effects of the Combination of Elranatamab (PF-06863135), Daratumumab, Lenalidomide or Elranatamab and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT05623020
- Lead Sponsor
- Pfizer
- Brief Summary
Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity. The main purpose of the study is to evaluate if the combination of Elranatamab, Daratumumab and Lenalidomide or Elranatamab and Lenalidomide offers superior clinical benefit compared with the combination of Daratumumab, Lenalidomide and Dexamethasone in people with multiple myeloma.
There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the minimal residual disease (MRD) negativity rate and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide or elranatamab and lenalidomide compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed transplant-ineligible multiple myeloma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1116
-
Diagnosis of multiple myeloma (MM) as defined by IMWG criteria (Rajkumar et al., 2014)
-
Measurable disease based on IMWG criteria as defined by at least 1 of the following:
- Serum M-protein ≥0.5 g/dL;
- Urinary M-protein excretion ≥200 mg/24 hours;
- Involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
-
Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.
-
Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant
-
ECOG performance status ≤2.
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Not pregnant and willing to use contraception
-
For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
- Smoldering Multiple Myeloma.
- Monoclonal gammopathy of undetermined significance.
- Waldenströms Macroglobulinemia
- Plasma cell leukemia.
- Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness.
- Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
- For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant ≤3 months prior to first dose of study intervention or active GVHD.
- For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, up to 4 days of 40 mg dexamethasone or equivalent before the first dose of study intervention).
- Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
- Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: Randomized Arm A: Elranatamab + Lenalidomide Elranatamab - Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide Lenalidomide - Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide Elranatamab - Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide Daratumumab - Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide Lenalidomide - Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide Lenalidomide - Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide Elranatamab - Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide Daratumumab - Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide Daratumumab - Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone Dexamethasone - Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone Lenalidomide - Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone Daratumumab - Part 1: Elranatamab + Lenalidomide Lenalidomide - Part 2: Randomized Arm A: Elranatamab + Lenalidomide Lenalidomide - Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide Elranatamab - Part 1: Elranatamab + Lenalidomide Elranatamab -
- Primary Outcome Measures
Name Time Method Part 1 Dose Limiting Toxicity From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab with daratumumab and lenalidomide Part 2: Progression free survival by blinded independent central review From randomization up to 79 months. Part 2: Minimal Residual Disease negativity rate At 12 months after randomization
- Secondary Outcome Measures
Name Time Method Overall minimal residual disease negativity rate From date of randomization up to 79 months PFS2 by investigator (Part 2) From the date of randomization up to 79 months Objective Response Rate From the date of randomization up to 79 months Complete Response Rate From the date of randomization up to 79 months Time to Response From the date of randomization to date of confirmed objective response up to 79 months Duration of Response From the date of confirmed objective response up to 79 months Duration of minimal residual disease negativity (Part 2) From date of minimal residual disease negative status up to 79 months Frequency of abnormal laboratory results From the date of first dose of study intervention up to 79 months Sustained MRD negativity rate (Part 2) From date of randomization up to 79 months PFS by investigator From date of randomization up to 79 months Duration of Complete Response From the date of confirmed complete response up to 79 months Frequency of treatment-emergent adverse events From the date of first dose of study intervention up to 79 months Pharmacokinetics of elranatamab when used in the elranatamab + daratumumab + lenalidomide or elranatamab + lenalidomide combinations From date of first dose of study intervention up to 79 months Predose and post dose concentrations of elranatamab
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (Part 2) From date the informed consent is signed up to 79 months Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the symptom scales/items represent a greater presence of symptoms.
Overall Survival From date of randomization up to 79 months Incidence of Anti-Drug Antibody and Neutralizing Antibody against elranatamab From date of first dose of study intervention up to 79 months Immunogenicity of elranatamab
Pharmacokinetics of daratumumab and lenalidomide when used in the elranatamab+daratumumab+lenalidomide or elranatamab+lenalidomide combinations (Part 1) From date of first dose of study intervention up to 79 months Predose concentrations of daratumumab and lenalidomide
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20 (Part 2) From date the informed consent is signed up to 79 months Higher scores on the functioning subscales (body image, future perspective) represent higher levels of functioning, whereas higher scores on the symptom subscales (disease symptoms, side effects) represent a greater presence of symptoms
Trial Locations
- Locations (63)
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch
🇨🇳Taoyuan, Taiwan
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Epworth Freemasons
🇦🇺Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
QEII Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Fakultní nemocnice Brno Bohunice
🇨🇿Brno, Brno-město, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Moravskoslezský KRAJ, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE
🇫🇷Toulouse, Haute-garonne, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, Vienne, France
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
🇫🇷Nantes, France
Universitaetsklinikum Tuebingen
🇩🇪Tübingen, Baden-württemberg, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Germany
Evangelismos General Hospital of Athens
🇬🇷Athens, Attikí, Greece
Alexandra General Hospital of Athens
🇬🇷Athens, Attikí, Greece
University Hospital of Ioannina
🇬🇷Ioannina, Ípeiros, Greece
Soroka Medical Center
🇮🇱Be'er Sheva, Hadarom, Israel
Rabin Medical Center
🇮🇱Petah-Tikva, Hamerkaz, Israel
The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric
🇮🇱Ramat Gan, Hamerkaz, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Tell Abīb, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
AUSL di Piacenza
🇮🇹Piacenza, Emilia-romagna, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Emilia-romagna, Italy
IRCCS Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, FG, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Lombardia, Italy
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
A.O.U. Policlinico Paolo Giaccone
🇮🇹Palermo, Sicilia, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Istituto Europeo di Oncologia IRCCS
🇮🇹Milano, Italy
ASL PESCARA-Presidio Ospedaliero Pescara
🇮🇹Pescara, Italy
AOU Policlinico Umberto I
🇮🇹Roma, Italy
University of Fukui Hospital
🇯🇵Yoshida-gun, Fukui, Japan
Gunma University Hospital
🇯🇵Maebashi, Gunma, Japan
Iwate Medical University Hospital
🇯🇵Yahaba-cho, Iwate, Japan
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi-cho, Shizuoka, Japan
Japanese Red Cross Medical Center
🇯🇵Shibuya-ku, Tokyo, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Yamagata University Hospital
🇯🇵Yamagata, Japan
Gachon University Gil Medical Center
🇰🇷Namdong-gu, Incheon-gwangyeoksi [incheon], Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Jeonranamdo, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Kyǒnggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Albert Schweitzer Ziekenhuis, locatie Dordwijk
🇳🇱Dordrecht, Zuid-holland, Netherlands
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
🇵🇱Wroclaw, Dolnośląskie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Pomorskie, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Śląskie, Poland
Institut Català d'Oncologia (ICO) - Badalona
🇪🇸Badalona, Barcelona [barcelona], Spain
Institut Català d'Oncologia - L'Hospitalet
🇪🇸L'Hospitalet Del Llobregat, Barcelona [barcelona], Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Catalunya [cataluña], Spain
Institut Català d'Oncologia (ICO) - Girona
🇪🇸Girona, Girona [gerona], Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario Doctor Peset
🇪🇸Valencia, València, Spain
Hospital San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan