Phase 3 Evaluation of Teclistamab with Lenalidomide versus Lenalidomide Monotherapy in Maintenance Therapy for Newly Diagnosed Multiple Myeloma Post-ASCT
- Trial ID
- 2023-510384-36-00
- Protocol
- EMN30
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 study is to compare the **efficacy** of **teclistamab** in combination with **lenalidomide** (Tec-Len) versus lenalidomide monotherapy (Len), and the efficacy of teclistamab monotherapy (Tec) versus lenalidomide monotherapy (Len) in the maintenance setting for patients with newly diagnosed **multiple myeloma**. This comparison is clinically relevant as it aims to assess progression-free survival (PFS) and 12-month minimal residual disease (MRD)-negative complete response (CR), which are critical indicators of treatment success and long-term patient outcomes.
Secondary objectives include:
- Further comparing the efficacy of Tec-Len to Len, and Tec to Len in the maintenance setting.
- Assessing the safety profile of maintenance Tec-Len and Tec.
- Characterizing the pharmacokinetics (PK) of maintenance Tec-Len and Tec.
- Assessing the immunogenicity of maintenance Tec-Len and Tec.
- Evaluating the impact of treatment with maintenance Tec-Len and Tec on patient-reported outcomes (PROs) compared with Len.
Participants
The clinical trial involves a total of **849 participants** diagnosed with **newly diagnosed multiple myeloma**. The study population includes both male and female subjects, aged **18 years and older**, who are not considered vulnerable populations. Participants were selected based on their recent diagnosis of symptomatic multiple myeloma and must have completed specific induction therapies. They are required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2, indicating they are in a generally good health status suitable for trial participation. Lifestyle considerations include adherence to specified contraceptive measures for both male and female participants, as well as compliance with other lifestyle restrictions outlined in the study protocol. The trial does not include individuals who have received maintenance therapy or those intolerant to the starting dose of lenalidomide. Participants must have achieved at least a partial response to their initial line of therapy and have completed high-dose chemotherapy and autologous stem cell transplantation within a specified timeframe. The sponsor has not provided additional information regarding specific lifestyle habits such as diet or physical activity.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **teclistamab** in combination with **lenalidomide** and as monotherapy compared to lenalidomide alone in patients with newly diagnosed multiple myeloma. This is a Phase 3, randomized, double-blind, controlled study. The trial aims to assess progression-free survival (PFS) and 12-month minimal residual disease (MRD)-negative complete response (CR) as primary endpoints. The study is expected to run until November 2031, with recruitment having commenced in September 2022.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, diagnosis, and previous treatment history. Following randomization, participants will receive either the combination therapy or monotherapy. Regular follow-up visits will be scheduled to monitor treatment efficacy and safety, including assessments of PFS, overall survival (OS), and adverse events (AEs). The end-of-study visit will conclude the participant's involvement, with final evaluations conducted to assess long-term outcomes.
The expected duration of participant involvement varies depending on the treatment arm, with a maximum treatment period of 24 months for lenalidomide and 1 month for teclistamab. Conditions that may lead to early termination from the study include significant adverse reactions, disease progression, or withdrawal of consent. Participants are required to adhere to specific lifestyle restrictions and contraceptive measures throughout the study to ensure safety and compliance with the protocol.
Treatment
The clinical trial involves the administration of **teclistamab**, a **solution for injection** of biological/biotechnological origin, specifically a BiTE (bispecific T-cell engager). Teclistamab is administered via **subcutaneous use**. The dosing schedule is based on a microgram per kilogram basis, although specific dosage amounts are not provided. The maximum treatment period for teclistamab is one month. Compliance with the administration schedule is monitored throughout the trial to ensure adherence to the protocol.
In addition to teclistamab, the trial includes the use of **Lenalidomide Accord** in various dosages: 2.5 mg, 5 mg, 10 mg, and 15 mg, all in the form of **hard capsules**. Lenalidomide is of chemical origin and is administered **orally**. The maximum treatment period for lenalidomide is 24 months. The trial compares the efficacy of teclistamab in combination with lenalidomide, teclistamab alone, and lenalidomide alone. Participant compliance with the oral administration of lenalidomide is also monitored to ensure accurate assessment of treatment efficacy.
Efficacy
The efficacy of the clinical trial will be assessed using dual primary endpoints: **Progression-Free Survival (PFS)** and 12-month **Minimal Residual Disease (MRD)-negative Complete Response (CR)**, both evaluated by an Independent Review Committee (IRC). Secondary endpoints include Overall Survival (OS), CR or better response, CR conversion, MRD-negative CR, MRD-negative conversion, sustained MRD-negative CR, PFS2, Time to Next Treatment (TTNT), incidence and severity of adverse events (AEs), pharmacokinetics (PK) of teclistamab, presence and activity of anti-drug antibodies (ADAs) to teclistamab, and changes in health-related quality of life (HRQoL), symptoms, and functioning.
The trial will compare the efficacy of teclistamab in combination with lenalidomide (Tec-Len) versus lenalidomide monotherapy (Len), and teclistamab monotherapy (Tec) versus lenalidomide monotherapy (Len) in the maintenance setting for participants with newly diagnosed **Multiple Myeloma**. The primary and secondary endpoints will be measured at various timepoints throughout the study, with specific focus on the 12-month MRD-negative CR and PFS. The study is designed to provide comprehensive data on the efficacy of the drug combinations in this patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 1.2 ≥18 years of age (and the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
- 2.3 Must have a new diagnosis of symptomatic MM according to IMWG criteria and have received 4 to 6 cycles of 3 or 4 drug-induction therapy that includes a proteasome inhibitor and/or an IMiD with or without anti-CD38 monoclonal antibody and a single or tandem ASCT. Post ASCT consolidation is permitted for up to 2 cycles as long as the total number of induction plus consolidation cycles does not exceed 6. Participants must complete all previous treatment prior to screening and at least 7 days prior to randomization (C1D1 for the safety run-in) except for cytotoxic therapy, which must be completed at least 21 days prior to randomization (C1D1 for the safety run-in).. SPEP from the time of diagnosis or prior to start of induction is required.
- 3.2 Must have received only one line of therapy and achieved at least a partial response (≥PR) as per IMWG 2016 response criteria based on the investigator's assessment. Participants with plasmacytomas at the time of diagnosis must meet IMWG 2016 response criteria . for ≥PR based on repeat imaging utilizing the same modality (Kumar 2016).
- 4 Must not be intolerant to the starting dose of lenalidomide.
- 5.3 Must have received high-dose chemotherapy and first ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT (7 months for participants who received consolidation) at the time of randomization or at the time of Sponsor approval for participants in safety run-in.
- Must not have received any maintenance therapy.
- 7.1 Have an ECOG performance status score of 0-2 at screening and immediately prior to the start of administration of study treatment.
- 8.1 Have clinical laboratory values meeting the following criteria (see the protocol).
- 9.1 A woman of childbearing potential must have a negative serum pregnancy test within 10-14 days prior to the start of study treatment and again either a serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
- 10.2 A woman must be: a)Not of childbearing potential, or b)Of childbearing potential practicing 2 reliable methods of contraception simultaneously including one highly effective method of contraception and one other effective method of contraception starting 4 weeks prior to dosing, throughout the study including during dose interruptions and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 6 months after the last dose of teclistamab, whichever occurs later. For participants who are of childbearing potential, see Section 6.11.3 for details regarding concomitant use of estrogen containing products and lenalidomide.
- 11.1 A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 6 months after the last dose of teclistamab, whichever occurs later.
- 12.2 A man must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 3 months after the last dose of teclistamab, whichever occurs later. If his female partner is of childbearing potential, the male participant must use condom (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception
- 13.2 A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 3 months after receiving the last dose of teclistamab, whichever occurs later
- 14 Must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
- 15.1 Must sign an informed consent form (ICF) (in accordance with the local requirements) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Exclusion Criteria
- Criterion 1 was deleted
- 2.1 Any previous therapy with a gene modified adoptive cell therapy
- 3 Discontinued treatment due to any AE related to lenalidomide as determined by the investigator
- 4.1 History of allogeneic stem cell transplantation or prior organ transplant
- 5.1 Progressive disease as per IMWG 2016 response criteria at any time prior to randomization or C1D1 for participants in the safety run in
- 6.1 Radiotherapy within 14 days or focal radiation within 7 days of C1D1
- 7.2 Received a cumulative dose of corticosteroids equivalent to > 40 mg of dexamethasone within the 14 days prior to C1D1
- 8.2 Received a live, attenuated vaccine within 4 weeks before C1D1. Non-live or non-replicating vaccines for emergency use are allowed
- 9.3 Excluded for any of the following a) Any ongoing myelodysplastic syndrome or B cell malignancy (other than MM) b) Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy c) Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured 1) Non-muscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, <3 cm, no CIS) 2) Non-melanoma skin cancers treated with curative therapy melanoma or localized melanoma treated with curative surgical resection alone 3) Non-invasive cervical cancer 4) Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer 5) Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only 6) Other malignancy that is considered cured with minimal risk of recurrence in consultation with the Sponsor's medical monitor
- 10.2 Plasma cell leukemia, smoldering multiple myeloma, Waldenström's macroglobulinemia, POEMS syndrome or light chain amyloidosis in the absence of underlying symptomatic myeloma as defined per IMWG criteria with the presence of CRAB and/or SLiM symptoms.
- 11 Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma.
- 12.1 Stroke, transient ischemic attack, or seizure within 6 months of C1D1
- 13 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients
- 14.1 Participant is pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug
- 15.1 Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
- 16.2 Presence of the following conditions: a)New York Heart Association stage III or IV congestive heart failure b)Myocardial infarction, unstable angina, or coronary artery bypass graft ≤6 months prior to C1D1 c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
- 17.1 Any of the following: a. HIV-positive participants with 1 or more of the following -History of AIDS-defining conditions -CD4 count <350 cells/mm3 at screening -Detectable viral load during screening or within six months prior to screening -Not receiving highly active ART -Had a change in antiretroviral therapy within 6 months of the start of screening -Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Medical Monitor
- 18.1 Hepatitis B infection: In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status
- 19.1 Active hepatitis C infection as measured by detectable HCV- RNA Testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic HCV infection completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study
- 20.3 Concurrent medical or psychiatric condition or disease, that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
- 21.1 Participant had major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or has not fully recovered from an earlier surgery, or has major surgery planned during the time the participant is expected to participate in the study or within 2 weeks after administration of the last dose of study treatment
- 22.1 Have received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks or 5 PK half-lives, whichever is longer, before C1D1 or is currently enrolled in an interventional investigational study except if only long term survival data is collected and after Sponsor approval is obtained
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 08 Sept 2022 | 100 |
 Belgium | Recruiting | 08 Sept 2022 | 50 |
 Czechia | Recruiting | 08 Sept 2022 | 100 |
 Denmark | Recruiting | 08 Sept 2022 | 60 |
 France | Recruiting | 08 Sept 2022 | 100 |
 Germany | Recruiting | 08 Sept 2022 | 80 |
 Greece | Recruiting | 08 Sept 2022 | 80 |
 Ireland | Recruiting | 08 Sept 2022 | 60 |
 Italy | Recruiting | 08 Sept 2022 | 300 |
 The Netherlands | Recruiting | 08 Sept 2022 | — |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Lenalidomide Accord 10 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 00 | 24 | PRD6773397 |
teclistamab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 00 | 1 | PRD9936207 |
Lenalidomide Accord 5 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 00 | 24 | PRD6773394 |
teclistamab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 00 | 1 | PRD9936206 |
Lenalidomide Accord 15 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 00 | 24 | PRD6773399 |
Lenalidomide Accord 2.5 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 00 | 24 | PRD6773391 |