Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Myeloma Network B.V., Emn Trial Office S.r.l. Impresa Sociale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Sep 2022 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Janssen Research & Development, LLC

External identifiers

EU CT number

2023-510384-36-00

EudraCT number

2021-002531-27

ClinicalTrials.gov

NCT05243797

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Therapy, Pharmacokinetic, Pharmacoeconomic, Others, Efficacy

To compare the efficacy of teclistamab in combination with lenalidomide (Tec-Len) with that of lenalidomide monotherapy (Len), and the efficacy of teclistamab monotherapy (Tec) with that of lenalidomide monotherapy (Len) in the maintenance setting as assessed by PFS and 12-month MRD-negative CR.

Secondary objectives 5

1. To further compare the efficacy of Tec-Len to Len, and the efficacy of Tec to Len in the maintenance setting.
2. To assess the safety profile of maintenance Tec-Len and Tec
3. To characterize the PK of maintenance Tec-Len and Tec
4. To assess the immunogenicity of maintenance Tec-Len and Tec
5. To evaluate the impact of treatment with maintenance Tec-Len and Tec on PROs compared with Len

Conditions and MedDRA coding

Newly Diagnosed Multiple Myeloma

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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. 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. 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. 4 Must not be intolerant to the starting dose of lenalidomide.
5. 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.
6. 6. Must not have received any maintenance therapy.
7. 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. 8.1 Have clinical laboratory values meeting the following criteria (see the protocol).
9. 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. 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. 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. 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. 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. 14 Must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
15. 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 22

1. Criterion 1 was deleted
2. 2.1 Any previous therapy with a gene modified adoptive cell therapy
3. 3 Discontinued treatment due to any AE related to lenalidomide as determined by the investigator
4. 4.1 History of allogeneic stem cell transplantation or prior organ transplant
5. 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. 6.1 Radiotherapy within 14 days or focal radiation within 7 days of C1D1
7. 7.2 Received a cumulative dose of corticosteroids equivalent to > 40 mg of dexamethasone within the 14 days prior to C1D1
8. 8.2 Received a live, attenuated vaccine within 4 weeks before C1D1. Non-live or non-replicating vaccines for emergency use are allowed
9. 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. 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. 11 Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma.
12. 12.1 Stroke, transient ischemic attack, or seizure within 6 months of C1D1
13. 13 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients
14. 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. 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. 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. 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. 18.1 Hepatitis B infection: In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status
19. 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. 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. 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. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS (per IRC) and 12-month MRD-negative CR (per IRC) are the dual primary endpoints for the study.

Secondary endpoints 12

1. OS is defined as the time from the date of randomization to the date of the participant’s death due to any cause.
2. CR or better (sCR+CR) is defined as participants who achieve a CR or better response per IMWG criteria.
3. CR conversion is defined as participants who were not in CR or better at the time of randomization but later went on to achieve CR or better prior to progressive disease or subsequent therapy, whichever is earlier.
4. MRD-negative CR is defined as participants who achieve CR or better and MRD-negative status, as determined by NGF with sensitivity of 10-5, prior to progressive disease or subsequent therapy, whichever is earlier.
5. MRD-negative conversion is defined as participants who have not achieved MRD-negative status at the time of randomization and who later achieved MRD-negative, prior to progressive disease or subsequent therapy, whichever is earlier.
6. Sustained MRD-negative CR is defined as participants who achieve MRD-negative CR, confirmed minimum 1 year apart and without any examination showing MRD-positive status in between.
7. PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first. Those who are alive and for whom a second disease progression has not been observed will be censored at the last date of follow-up.
8. TTNT is defined as the time from randomization to the start of subsequent antimyeloma treatment. Death due to progressive disease without start of subsequent therapy will be considered as event. Participants who withdrew full consent to study or are lost to follow-up, or die due to causes other than disease progression will be censored at the date of death or the last date known to be alive.
9. Incidence and severity of AEs
10. The PK of teclistamab.
11. Presence and activity of ADAs to teclistamab
12. Time to worsening in overall HRQoL, symptoms, and functioning Change from baseline in overall HRQoL, symptoms, and functioning

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Myeloma Network B.V.

Sponsor organisation

European Myeloma Network B.V.

Address

Blaak 555

City

Rotterdam

Postcode

3011 GB

Country

Netherlands

Scientific contact point

Organisation

European Myeloma Network B.V.

Contact name

Prof. Elena Zamagni

Public contact point

Organisation

European Myeloma Network B.V.

Contact name

Prof. Pieter Sonneveld

Third parties 17

Emn Trial Office S.r.l. Impresa Sociale

Sponsor organisation

Emn Trial Office S.r.l. Impresa Sociale

Address

Via Saluzzo 1/a, TO

City

Turin

Postcode

10125

Country

Italy

Scientific contact point

Organisation

Emn Trial Office S.r.l. Impresa Sociale

Contact name

Prof. Mario Boccadoro

Public contact point

Organisation

Emn Trial Office S.r.l. Impresa Sociale

Contact name

Prof. Mario Boccadoro

Sponsor responsibilities

Article 77 compliance

European Myeloma Network B.V.

Contact point sponsor

European Myeloma Network B.V.

Article 77 implementation

European Myeloma Network B.V.

Locations

13 EU/EEA countries · 97 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 160 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications