HumRes63060
|
SNCTP000005550
|
BASEC2023-00172
|
EUCTR2021-000803-20
MagnetisMM-6: A Phase III Study of Elranatamab (PF-06863135) + Daratumumab + Lenalidomide Compared to Daratumumab + Lenalidomide + Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma Who Are Not Eligible for Transplantation
Summary description of the study
1.1. Synopsis This is an open-label, two-arm, multicenter, randomized Phase III study to assess the efficacy and safety of Elranatamab (PF-06863135) + Daratumumab + Lenalidomide (EDR) compared to Daratumumab + Lenalidomide + Dexamethasone (DRd) in participants who are not eligible for transplantation. The randomized Phase III part of the study (Part 2 with participants with newly diagnosed Multiple Myeloma) is preceded by Part 1. Patients are invited to participate in Part 2, where the combination of study drugs investigated in Part 1 (referred to as EDR) is compared to the study drug combination of Daratumumab (D), Lenalidomide (R), and Dexamethasone (d) (this combination is referred to as DRd) to determine which combination is better suited for the treatment of Multiple Myeloma.
(BASEC)
Intervention under investigation
For this study, patients must visit the investigator every week for the first 6 months of treatment, and then every 2 weeks if possible, to undergo study procedures. These procedures include blood, bone marrow, urine, and saliva sampling, imaging procedures, ECGs, physical and neurological examinations, as well as answering health questions using electronic devices (tablet computers). A hospital stay is required when the study medication is administered for the first and second time.
Patients are asked to participate in the study for approximately 5 years.
(BASEC)
Disease under investigation
MULTIPLE MYELOMA
(BASEC)
Criteria for participation in trial
Age and sex: 1. Participants aged ≥ 18 years (or country-specific minimum age for consent, if > 18 years) at Visit 1 (screening). • Male participants and females of childbearing potential must consent to use contraceptive methods, as described in Section 5.3.1 of the study protocol. • A woman is eligible to participate if she is not pregnant or breastfeeding. • The criteria for reproductive capability of male participants (Section 10.4.1 of the protocol) and female participants (Section 10.4.2 of the protocol) are listed in Appendix 4. Type of participants and disease characteristics: 2. Diagnosis of MM according to IMWG criteria (Rajkumar et al., 2014), including measurable disease based on IMWG criteria, defined by at least one of the following points (as assessed by the central laboratory for Part 2): o M-Protein in serum ≥ 0.5 g/dl; o Excretion of M-Protein in urine ≥ 200 mg/24 hours; o With FLC ≥ 10 mg/dl (≥ 100 mg/l) AND abnormal ratio of Kappa to Lambda-FLC in serum immunoglobulin (< 0.26 or > 1.65). Part 2 only: The participant has NDMM and is not eligible for transplantation. This is the case if the age is ≥ 65 years or if at an age of < 65 years there are comorbidities that limit the possibility of transplantation. 4. ECOG Performance Status ≤ 2. 5. BM function characterized by: a. ANC ≥ 1.0 × 10^9/l (the use of G-CSF is allowed if completed at least 7 days before the planned start of administration); b. Platelet count ≥ 75,000/μl, if < 50% of the nucleated cells in the BM are plasma cells, or ≥ 50,000/μl, if ≥ 50% of the nucleated cells in the BM are plasma cells (transfusion support is allowed if completed at least 7 days before the planned start of administration); and c. Hemoglobin ≥ 8 g/dl (transfusion support is allowed if completed at least 14 days before the planned start of administration). 6. Corrected serum calcium ≤ 14 mg/dl (≤ 3.5 mmol/l) or free ionized calcium ≤ 6.5 mg/dl (≤ 1.6 mmol/l). (BASEC)
Exclusion criteria
Diseases/medical complications: 1. Smoldering Multiple Myeloma or monoclonal gammopathy of undetermined significance or Waldenström's macroglobulinemia or plasma cell leukemia, defined as ≥ 20% circulating plasma cells in peripheral blood with an absolute plasma cell count of more than 2 × 10^9/l or systemic light chain amyloidosis or POEMS syndrome. 2. Impairment of cardiovascular function or clinically significant cardiovascular diseases, defined as one of the following within 6 months prior to enrollment: a. Acute myocardial infarction or acute coronary syndromes (e.g., unstable angina, coronary artery bypass, coronary angioplasty or coronary stenting, symptomatic pericardial effusion); b. Clinically significant arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); c. Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis [except when associated with complication from ZKV] or pulmonary embolism); d. Long QT syndrome (or QTcF > 470 ms at screening). e. LVEF < 40%, determined by a MUGA scan or echocardiogram. 3. Persistent peripheral sensory or motor neuropathy of grade 3 or higher, history of Guillain-Barré syndrome or GBS variants or history of peripheral motor polyneuropathy of grade > 3. 4. Participants with active, uncontrolled bacterial, fungal, or viral infections, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness. Active infections must have resolved at least 14 days prior to enrollment. Comments on specific circumstances will follow. a. HIV: In doubtful cases, participants with negative viral load may be eligible. HIV-positive participants who are otherwise healthy and at low risk for AIDS-related consequences may be considered eligible. The potential eligibility of a specific HIV-positive study candidate should be assessed prior to screening based on current and past CD4 and T-cell counts, history (if any) of AIDS-specific illnesses (e.g., opportunistic infections), and HIV treatment status, and discussed with the sponsor. Additionally, the potential for drug interactions is considered. b. HBV/HCV: Relevant laboratory tests should be performed at screening. For further details, please refer to the CDC website (https://www.cdc.gov/hepatitis/index.htm). c. HBV: • This criterion excludes participants with a positive HBsAg test (i.e., either acute or chronic active hepatitis). • Participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are however eligible. • Participants with a positive Anti-HBcAb but negative HBsAg and Anti-HBsAb profile are eligible if no HBV DNA is detected. d. HCV: • A positive HCV antibody indicates an infection but does not necessarily mean that a potential participant is no longer eligible. This depends on clinical circumstances. If contact with HCV has occurred recently, HCV antibodies may not yet be positive. In this case, it is advisable to test for HCV RNA. For further details, please refer to the CDC website (https://www.cdc.gov/hepatitis/hcv/pdfs/hcv_graph.pdf). 5. Any other active malignant tumor within 3 years prior to study enrollment, except adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ, or stage 0/1 with minimal risk of recurrence as assessed by the investigator. 6. Participants with known or suspected hypersensitivity to the study interventions or any of their other components. 7. Participants with known or suspected CNS involvement or with clinical signs of myelomatous meningeal involvement. 8. Other surgical (including major surgical procedures within 14 days prior to study enrollment), medical, or psychiatric conditions, including new (within the last year) or active suicidal thoughts or active suicidal behavior or laboratory abnormalities that may increase the risk of study participation or, in the opinion of the investigator, render the participant unsuitable for the study. • Active inflammatory bowel disease, chronic diarrhea, known diverticular disease, or previous gastric resection or laparoscopic sleeve gastrectomy. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (provided there is no potential for interactions with other medications). 11. Part 2 only: Previous systemic treatment for MM except for a short course of corticosteroids (i.e., up to 4 days with 40 mg Dexamethasone or equivalent prior to the first dose of the study intervention). 12. Live attenuated vaccine administered within 4 weeks prior to the first dose of the study intervention (see Section 6.8 of the protocol). (BASEC)
Age and sex: 1. Participants aged ≥ 18 years (or country-specific minimum age for consent, if > 18 years) at Visit 1 (screening). • Male participants and females of childbearing potential must consent to use contraceptive methods, as described in Section 5.3.1 of the study protocol. • A woman is eligible to participate if she is not pregnant or breastfeeding. • The criteria for reproductive capability of male participants (Section 10.4.1 of the protocol) and female participants (Section 10.4.2 of the protocol) are listed in Appendix 4. Type of participants and disease characteristics: 2. Diagnosis of MM according to IMWG criteria (Rajkumar et al., 2014), including measurable disease based on IMWG criteria, defined by at least one of the following points (as assessed by the central laboratory for Part 2): o M-Protein in serum ≥ 0.5 g/dl; o Excretion of M-Protein in urine ≥ 200 mg/24 hours; o With FLC ≥ 10 mg/dl (≥ 100 mg/l) AND abnormal ratio of Kappa to Lambda-FLC in serum immunoglobulin (< 0.26 or > 1.65). Part 2 only: The participant has NDMM and is not eligible for transplantation. This is the case if the age is ≥ 65 years or if at an age of < 65 years there are comorbidities that limit the possibility of transplantation. 4. ECOG Performance Status ≤ 2. 5. BM function characterized by: a. ANC ≥ 1.0 × 10^9/l (the use of G-CSF is allowed if completed at least 7 days before the planned start of administration); b. Platelet count ≥ 75,000/μl, if < 50% of the nucleated cells in the BM are plasma cells, or ≥ 50,000/μl, if ≥ 50% of the nucleated cells in the BM are plasma cells (transfusion support is allowed if completed at least 7 days before the planned start of administration); and c. Hemoglobin ≥ 8 g/dl (transfusion support is allowed if completed at least 14 days before the planned start of administration). 6. Corrected serum calcium ≤ 14 mg/dl (≤ 3.5 mmol/l) or free ionized calcium ≤ 6.5 mg/dl (≤ 1.6 mmol/l). (BASEC)
Exclusion criteria
Diseases/medical complications: 1. Smoldering Multiple Myeloma or monoclonal gammopathy of undetermined significance or Waldenström's macroglobulinemia or plasma cell leukemia, defined as ≥ 20% circulating plasma cells in peripheral blood with an absolute plasma cell count of more than 2 × 10^9/l or systemic light chain amyloidosis or POEMS syndrome. 2. Impairment of cardiovascular function or clinically significant cardiovascular diseases, defined as one of the following within 6 months prior to enrollment: a. Acute myocardial infarction or acute coronary syndromes (e.g., unstable angina, coronary artery bypass, coronary angioplasty or coronary stenting, symptomatic pericardial effusion); b. Clinically significant arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); c. Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis [except when associated with complication from ZKV] or pulmonary embolism); d. Long QT syndrome (or QTcF > 470 ms at screening). e. LVEF < 40%, determined by a MUGA scan or echocardiogram. 3. Persistent peripheral sensory or motor neuropathy of grade 3 or higher, history of Guillain-Barré syndrome or GBS variants or history of peripheral motor polyneuropathy of grade > 3. 4. Participants with active, uncontrolled bacterial, fungal, or viral infections, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness. Active infections must have resolved at least 14 days prior to enrollment. Comments on specific circumstances will follow. a. HIV: In doubtful cases, participants with negative viral load may be eligible. HIV-positive participants who are otherwise healthy and at low risk for AIDS-related consequences may be considered eligible. The potential eligibility of a specific HIV-positive study candidate should be assessed prior to screening based on current and past CD4 and T-cell counts, history (if any) of AIDS-specific illnesses (e.g., opportunistic infections), and HIV treatment status, and discussed with the sponsor. Additionally, the potential for drug interactions is considered. b. HBV/HCV: Relevant laboratory tests should be performed at screening. For further details, please refer to the CDC website (https://www.cdc.gov/hepatitis/index.htm). c. HBV: • This criterion excludes participants with a positive HBsAg test (i.e., either acute or chronic active hepatitis). • Participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are however eligible. • Participants with a positive Anti-HBcAb but negative HBsAg and Anti-HBsAb profile are eligible if no HBV DNA is detected. d. HCV: • A positive HCV antibody indicates an infection but does not necessarily mean that a potential participant is no longer eligible. This depends on clinical circumstances. If contact with HCV has occurred recently, HCV antibodies may not yet be positive. In this case, it is advisable to test for HCV RNA. For further details, please refer to the CDC website (https://www.cdc.gov/hepatitis/hcv/pdfs/hcv_graph.pdf). 5. Any other active malignant tumor within 3 years prior to study enrollment, except adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ, or stage 0/1 with minimal risk of recurrence as assessed by the investigator. 6. Participants with known or suspected hypersensitivity to the study interventions or any of their other components. 7. Participants with known or suspected CNS involvement or with clinical signs of myelomatous meningeal involvement. 8. Other surgical (including major surgical procedures within 14 days prior to study enrollment), medical, or psychiatric conditions, including new (within the last year) or active suicidal thoughts or active suicidal behavior or laboratory abnormalities that may increase the risk of study participation or, in the opinion of the investigator, render the participant unsuitable for the study. • Active inflammatory bowel disease, chronic diarrhea, known diverticular disease, or previous gastric resection or laparoscopic sleeve gastrectomy. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (provided there is no potential for interactions with other medications). 11. Part 2 only: Previous systemic treatment for MM except for a short course of corticosteroids (i.e., up to 4 days with 40 mg Dexamethasone or equivalent prior to the first dose of the study intervention). 12. Live attenuated vaccine administered within 4 weeks prior to the first dose of the study intervention (see Section 6.8 of the protocol). (BASEC)
Trial sites
Aarau, Bern, Chur, Lausanne, Winterthur, Zurich
(BASEC)
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Poland, Spain, Sweden, Switzerland, T?rkiye, Taiwan, United Kingdom, United States (ICTRP)
Sponsor
Martina Knecht Maier Pfizer AG
(BASEC)
Contact
Contact Person Switzerland
Martina Knecht Maier
+41 78 615 62 56
martina.knechtmaier@clutterpfizer.comPfizer AG
(BASEC)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
26.06.2023
(BASEC)
ICTRP Trial ID
EUCTR2021-000803-20 (ICTRP)
Official title (approved by ethics committee)
MAGNETISMM-6: AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE OR TRANSPLANT-DEFERRED PARTICIPANTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (BASEC)
Academic title
An Open-Label, 2-Arm, Multicenter, Randomized Phase 3 Study To Evaluate The Efficacy And Safety of Elranatamab (PF-06863135) + Daratumumab + Lenalidomide Versus Daratumumab + Lenalidomide + Dexamethasone in Transplant-Ineligible Participants With Newly-Diagnosed Multiple Myeloma (ICTRP)
Public title
MagnetisMM-6: A Phase 3 Study of Elranatamab (PF-06863135) + Daratumumab + Lenalidomide Versus Daratumumab + Lenalidomide + Dexamethasone in Transplant-Ineligible Participants With Newly-Diagnosed Multiple Myeloma (ICTRP)
Disease under investigation
Multiple myeloma
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)
Intervention under investigation
Product Name: Elranatamab
Product Code: PF-06863135
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Elranatamab
Current Sponsor code: PF-06863135
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-
Trade Name: DARZALEX 1800 mg solution for injection
Product Name: Daratumumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Daratumumab
CAS Number: 945721-28-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
Product Name: Lenalidomide 5 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Product Name: Dexamethasone 20 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
Other descriptive name: Dexamethasone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Product Name: Lenalidomide 10 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Product Name: Lenalidomide 15 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Product Name: Lenalidomide 20 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Product Name: Lenalidomide 25 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrat (ICTRP)
Type of trial
Interventional clinical trial of medicinal product (ICTRP)
Trial design
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)
Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes
Inclusion criteria:
Participants must meet the following inclusion criteria to be eligible for
enrollment into the study. Criteria are for both Part 1 and Part 2 unless otherwise specified:
Age and Sex:
?Participant's age =18 years (or the minimum country specific age of
consent if >18) at Visit 1 (Screening).
Type of Participant and Disease Characteristics:
?Diagnosis of multiple myeloma (MM) as defined according to IMWG criteria.
?Measurable disease based on IMWG criteria as defined by at least 1 of
the following (as assessed by the central laboratory for Part 2):
?Serum M-protein =0.5 g/dL;
?Urinary M-protein excretion =200 mg/24 hours;
?Involved free light chain (FLC) =10 mg/dL (=100 mg/L) AND abnormal
serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
?Part 1 only: Participant with NDMM or RRMM. NDMM participant must
be transplant-ineligible as defined by age =65 years or transplantineligible
as defined by age <65 years with comorbidities impacting the
possibility of transplant. Participants with RRMM must have received 1-2
prior lines of MM therapy including at least one immunomodulatory drug
(IMiD) and one proteasome inhibitor (PI).
Part 2 only: Participant has NDMM and is transplant-ineligible as defined by age =65 years or is transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.
?Eastern Cooperative Oncology Group (ECOG) performance status =2.
?Adequate hepatic, renal, and bone marrow (BM) function (absolute
neutrophil count [ANC], platelet count, hemoglobin).
?Corrected serum calcium =14 mg/dL (=3.5 mmol/L), or free ionized calcium =6.5 mg/dL (=1.6 mmol/L).
?Resolved acute effects of any prior therapy to baseline severity or
CTCAE Grade =1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1100
(ICTRP)
Exclusion criteria:
Medical Conditions:
?Smoldering MM.
?Monoclonal gammopathy of undetermined significance (MGUS).
?Plasma cell leukemia.
?Waldenstr?ms Macroglobulinemia.
?Systemic light chain amyloidosis.
?Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal
gammopathy, and Skin abnormalities (POEMS) Syndrome.
?Impaired cardiovascular function or clinically significant cardiovascular
diseases within 6 months prior to enrollment.
?Ongoing Grade 3 or higher peripheral sensory or motor neuropathy,
history of Guillain-Barr? syndrome (GBS) or GBS variants, or history of
any Grade >3 peripheral motor polyneuropathy.
?Active, uncontrolled bacterial, fungal, or viral infection, including (but
not limited to) coronavirus disease 2019 (COVID-19)/severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis B virus
(HBV), hepatitis C virus (HCV), and known human immunodeficiency
virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related
illness. Active infections must be resolved at least 21 days prior to
enrollment. Participants treated with systemic anti-infective agents
within 28 days prior to enrollment are not eligible. Prophylactic use of systemic agents is permitted.
?Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator
?Participants with known or suspected hypersensitivity to the study
interventions or any of their excipients.
?Participants with known or suspected central nervous system (CNS) or
clinical signs of myelomatous meningeal involvement.
?Other surgical (including major surgery within 14 days prior to
enrollment), medical or psychiatric conditions including recent (within
the past year) or active suicidal ideation/behaviour or laboratory
abnormality that may increase the risk of study participation or, in the
investigator's judgment, make the participant inappropriate for the
study.
?Active inflammatory gastrointestinal disease, chronic diarrhea, known
diverticular disease or previous gastric resection or lap band surgery.
Gastroesophageal reflux disease under treatment with proton pump
inhibitors is allowed (assuming no drug interaction potential).
Primary and secondary end points
Main Objective: Part 1
To assess dose limiting toxicities (DLTs) of EDR to select an RP3D for the
combination to be used in Part 2 of this study.
Part 2
To compare the efficacy of EDR (Arm A) vs DRd (Arm B) as measured by
MRD status and PFS;Secondary Objective: Part 1
?To evaluate the overall safety profile of EDR to select an RP3D for the
combination to be used in Part 2 of this study.
?To evaluate the efficacy of EDR to select an RP3D for the combination
to be used in Part 2 of this study.
?To evaluate the PK of elranatamab when used in combination with
daratumumab and lenalidomide
?To evaluate the immunogenicity of elranatamab when used in combination with daratumumab and lenalidomide
?To evaluate the PK of aratumumab and lenalidomide when used in combination with elranatamab
Part 2
Key Secondary: To compare the efficacy of EDR (Arm A) vs DRd (Arm B)as measured by OS.;Primary end point(s): Part 1
DLTs during the DLT observation period:
?For all dose levels (DLs) except DL F: From the first priming dose of
elranatamab in the 2 Step-up Priming Dose Period until 28 days (? visit windows) from the first administration of the EDR combination.
?For DL F: 28 days (? visit windows) from the day of the first full dose of
elranatamab (76 mg) in combination with daratumumab (D) and
lenalidomide (R.).
Part 2:
?Sustained MRD negativity rate (central lab) for at least 12 months per IMWG as assessed via next generation sequencing (NGS)
?PFS by blinded independent central review (BICR) per IMWG;Timepoint(s) of evaluation of this end point: Assessments are to be conducted at the time points specified in the Schedule of Activity (SoA) in Section 1 of the protocol (ICTRP)
Secondary end point(s): Part 1
?Adverse events (AEs) as characterized by type, frequency, severity (as
graded by National Cancer Institute Common Terminology Criteria for
Adverse Events [NCI CTCAE] v5.0), timing, seriousness, and relationship to study treatment. Severity of cytokine release syndrome (CRS) and
immune effector cell-associated neurotoxicity syndrome (ICANS) will be
graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
? Laboratory abnormalities as characterized by type, frequency, severity
(as graded by NCI CTCAE v5.0), and timing.
?Objective response rate (ORR) and complete response rate (CRR,), per
International Myeloma Working Group (IMWG) response criteria as
determined by investigator.
?Time to event endpoints: time to response (TTR, ), duration of response
(DOR, ), duration of complete response (DOCR) and progression-free survival (PFS) per IMWG response criteria as determined by
investigator, and overall survival (OS;);
?Minimal residual disease (MRD) negativity rate (central laboratory) per
IMWG sequencing criteria.
? Predose and post dose concentrations of elranatamab
? Anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs)
against elranatamab
? Predose concentrations of daratumumab and lenalidomide
Part 2
Key Secondary: OS
Secondary:
?Overall MRD negativity rate per IMWG
?Duration of MRD negativity per IMWG
?PFS and progression-free survival on next line of therapy (PFS2) by
investigator per IMWG
?ORR, CRR, TTR, DOR, and DOCR by BICR per IMWG
?AEs as characterized by type, frequency, severity (as graded by NCI
CTCAE v5.0), timing, seriousness, and relationship to study treatment.
The severity of CRS and ICANS will be graded according to ASTCT criteria (Lee, 2019).
? Laboratory abnormalities as characterized by type, frequency, severity
(as graded by NCI CTCAE v5.0), and timing.
? Predose and post dose concentrations of elranatamab.
? ADAs and NAbs against elranatamab.
? EORTC QLQ-C30 and MY20European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQC30) and Myeloma Module 20 (MY20).;Timepoint(s) of evaluation of this end point: Assessments are to be conducted at the time points specified in the Schedule of Activity (SoA) in Section 1 of the protocol (ICTRP)
Registration date
07.03.2023 (ICTRP)
Incorporation of the first participant
12.05.2023 (ICTRP)
Secondary sponsors
not available
Additional contacts
ClinicalTrials.gov Call Center, ClinicalTrials.gov_Inquiries@pfizer.com, +18007181021, Pfizer Inc. (ICTRP)
Secondary trial IDs
C1071006, 2021-000803-20-PL (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000803-20 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available