Study for frail patients with newly diagnosed multiple myeloma treated with Daratumumab in combination with Teclistamab and Talquetamab.

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

8 Jan 2026 → ongoing

Decision date (initial)

2025-10-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Janssen Research & Development, LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Efficacy

To determine the PFS at 18 months in patients treated with Tec-Dara (Cohort 1) or Tal-Dara (Cohort 2)

Secondary objectives 3

1. To assess the efficacy of fixed duration of Tec-Dara (Cohort 1) or Tal-Dara (Cohort 2).
2. To determine the response rate after re-treatment of Tec-Dara (Cohort 1) or Tal-Dara (Cohort 2).
3. To assess the safety and tolerability of Tec-Dara (Cohort 1) or Tal-Dara (Cohort 2).

Conditions and MedDRA coding

Newly Diagnosed Multiple Myeloma

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Patient is ≥18 years of age and capable of giving informed consent and must sign an informed consent form (ICF), indicating that they understand the purpose of, and procedures required for, the study and is willing to participate in the study
2. 2. Newly diagnosed and treatment-naïve patients with a confirmed diagnosis of MM with measurable disease according to IMWG criteria
3. 3. Measurable disease defined as M-protein in the serum (≥1 g/dL) or serum free light chain assay ≥10 mg/dL [≥100 mg/L] and abnormal serum immunoglobulin kappa/lambda FLC ratio
4. 4. Frail according to the Simplified IMWG frailty index
5. 5. Have clinical laboratory values meeting the following criteria (see protocol)
6. 6. Patients of childbearing potential must agree to use adequate/highly effective contraception from the time of signing the informed consent form through 3 months after the last dose of study drug

Exclusion criteria 17

1. 1. Non-secretory MM or measurable disease by urine or plasmacytoma only
2. 2. Central nervous system involvement of myeloma or presence of the following heart conditions: a. Severe cardiac dysfunction (NYHA classification III-IV) b. Myocardial infarction, unstable angina, or coronary artery bypass graft ≤6 months prior to eligibility c. History of clinically significant ventricular arrhythmia d. Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities e. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >500 msec f. Screening ECHO or MUGA: left ventricular ejection fraction (LVEF) <35%
3. 3. Significant pulmonary dysfunction defined as: a. Acute diffuse infiltrative pulmonary disease. b. COPD with Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal or diffusing capacity of the lungs for carbon monoxide [DLCO] <50%. (Note that FEV1 testing is required for patients suspected of having COPD and patients must be excluded if FEV1<50 of predicted normal). c. Moderate or severe persistent asthma within the past 2 years or currently uncontrolled asthma of any classification. (Note that patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
4. 4. Stroke, transient ischemic attack, or seizure within 6 months of eligibility.
5. 5. Evidence of active systemic viral, fungal, or bacterial infections, requiring systemic antimicrobial therapy.
6. 6. Any of the following infections: a. Seropositive for Human Immunodeficiency Virus (HIV). b. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). c. Seropositive for hepatitis C (anti-HCV antibody positive or HCV-RNA quantitation positive).
7. 7. Exclude for any of the following: a. Any history of malignancy other than MM which is considered at high risk of recurrence requiring treatment or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity. b. 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: i. Non-muscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, <3 cm, no CIS) ii. Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone iii. Non-invasive cervical cancer iv. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer (anti-hormonal therapy is permitted) v. Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment) vi. Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor’s medical monitor.
8. 8. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before eligibility. Exception: a. Vitiligo not on systemic therapy b. Controlled Type 1 diabetes c. Prior autoimmune thyroid disease that is currently euthyroid based on clinical symptoms and laboratory testing
9. 9. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients (refer to IB and most recently applicable RSI).
10. 10. Extensive radiotherapy within 14 days or focal radiation only within 7 days of eligibility.
11. 11. Current or active therapy for multiple myeloma or received a cumulative dose corticosteroids equivalent to >40 mg dexamethasone within the 14 days prior to C1D1.
12. 12. Received a live attenuated vaccine ≤4 weeks before eligibility. Non-live vaccines or non-replicating authorized for emergency use (eg, COVID-19) are allowed.
13. 13. Received a strong CYP3A4 inducer or use of St. John’s wort ≤5 half-lives prior to dosing.
14. 14. Patient had major surgery or significant traumatic injury within 2 weeks prior to eligibility. Kyphoplasty or Vertebroplasty is not considered major surgery.
15. 15. Have received an investigational drug (including investigation vaccines) or used an invasive investigational medical device <4 week or 5 PK half-lives, before eligibility or is currently enrolled in an interventional investigational study except if only long-term survival data are collected
16. 16. Concurrent medical or psychiatric condition or disease (eg, uncontrolled diabetes, alcohol or drug abuse, severe dementia or altered mental status), that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participation in the study.
17. 17. Any other issue that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (eg,, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS at 18 months, defined as the duration from the date of randomization to first documented PD, or death, whichever occurs first.

Secondary endpoints 3

1. Secondary efficacy endpoints: ● PFS ● OS ● MRD negativity rate at 18 months and over time ● MRD-negative CR at 18 months and over time ● Sustained MRD-negative CR (≥12 months) ● Depth of response defined by the ORR and the rate of sCR, CR, VGPR and PR ● Time to partial response and time to best response ● EFS, with events defined as: PD, death, treatment discontinuation due to toxicity ● PFS2 from the date of randomization to 2nd PD or death, whichever comes first ● TNT
2. ● Depth of response defined by the ORR (sCR, CR, VGPR and PR) after re-treatment ● MRD-negativity rate after re-treatment
3. ● Incidence and severity of AEs during initial therapy, TFI and after restarting therapy ● Discontinuation rate due to treatment related toxicity during initial therapy and after restarting therapy, including overall discontinuation rate, discontinuation rate of daratumumab, teclistamab and talquetamab ● Causes of discontinuation of therapy during initial therapy and after restarting therapy ● Incidence, grade and cause of infections [...] (for more information, refer to the protocol)

Investigational products

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

Test 5

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. Dr. Sonja Zweegman

Public contact point

Organisation

European Myeloma Network B.V.

Contact name

Prof. Pieter Sonneveld

Third parties 8

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

4 EU/EEA countries · 29 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 61 files

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

Application history

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