Talquetamab for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- 18 to 70 years of age, inclusive"}
• {"criterion_text":"- Willing and able to adhere to the lifestyle restrictions specified in this protocol"}
• {"criterion_text":"- Participant must have documented MM satisfying the IMWG criteria and measurable disease"}
• {"criterion_text":"- Newly diagnosed patients eligible for high dose therapy and ASCT"}
• {"criterion_text":"- ECOG performance status score ≤2"}
• {"criterion_text":"- Hemoglobin ≥8 g/dL (5 mmol/L; RBC transfusion allowed; recombinant human erythropoietin use is permitted)"}
• {"criterion_text":"- Platelets ≥75×109/L in participants in whom <50% of bone marrow nucleated cells are plasma cells and ≥50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test)"}
• {"criterion_text":"- ANC >=1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated G-CSF)"}
• {"criterion_text":"- AST and ALT ≤2.5×ULN"}
• {"criterion_text":"- eCFR ≥30 mL/min based on Modified Diet in Renal Disease 4-variable Formula calculation (Appendix )"}
• {"criterion_text":"- Total Bilirubin <1.5×ULN (isolated total bilirubin ≥1.5×ULN with conjugated [direct] bilirubin <1.5×ULN is allowed for those participants with known Gilbert’s syndrome)"}
• {"criterion_text":"- HIV-positive participants are eligible if they meet all of the following: a. No detectable viral load (ie, <50 copies/mL) at screening b. CD4+ count >300 cells/mm3 at screening c. No AIDS-defining opportunistic infection within 6 months of screening d. Receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening. e. NOTE: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment)"}
• {"criterion_text":"- A female participant of childbearing potential must have a negative highly sensitive serum (β hCG) pregnancy test at screening, again a negative serum test within 24 hours prior to the start of study treatment and must agree to further urine or serum pregnancy tests during the study and within 100 days after receiving the last dose of study treatment."}
• {"criterion_text":"- A female participant must be (as defined in Appendix 5): • Not of childbearing potential, or • Of childbearing potential and 1) Practicing true abstinence; or2) Have a sole partner who is vasectomized; or 3) Practicing 2 effective methods of contraception (at least 1 highly‑effective, method of contraception"}
• {"criterion_text":"- A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment"}
• {"criterion_text":"- A male participant 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 100 days after receiving the last dose of study treatment. If a male participant’s partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception"}
• {"criterion_text":"- A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment."}
• {"criterion_text":"- Must sign an ICF (or their LAR must sign) 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_text":"- Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light chain amyloidosis"}
• {"criterion_text":"- Hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status see Section 8.5.5.1 for further required assessments."}
• {"criterion_text":"- Active hepatitis C infection as measured by positive HCV-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA for at least 12 weeks following the completion of therapy, the participant is eligible for the study."}
• {"criterion_text":"- Prior or current systemic therapy or stem cell transplantation for any plasma cell dyscrasia, with the exception of emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment. a. Plasmapheresis within 28 days of enrollment. b. Radiation therapy within 14 days of C1D1 or local radiation within 7 days of C1D1"}
• {"criterion_text":"- Major surgery within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment"}
• {"criterion_text":"- Contraindications to the use of Dara-VRd per SmPC."}
• {"criterion_text":"- Taken any disallowed therapies before the planned first dose of study treatment"}
• {"criterion_text":"- Prior or concurrent exposure to any of the following, in the specified time frame prior to first dose of study treatment: a. Investigational vaccine other than SARS-CoV-2 vaccine approved/in use under emergency approval within 4 weeks. Non-live or non-replicating vaccines authorized for emergency use (eg, COVID-19) by local health authorities are allowed. b. Live, attenuated vaccine within 4 weeks c. Monoclonal antibody therapy within 21 days (not used for the treatment of MM)"}
• {"criterion_text":"- Received a strong CYP3A4 inducer within 5 half-lives prior to start of administration of study treatment"}
• {"criterion_text":"- Participant is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment"}
• {"criterion_text":"- Participant plans to father a child while enrolled in this study or within 6 months after the last dose of study treatment"}
• {"criterion_text":"- Known active CNS involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain MRI and lumbar cytology are required"}
• {"criterion_text":"- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI-CTCAE Version 5"}
• {"criterion_text":"- 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 MM, 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 MM. 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 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 (anti-hormonal therapy is permitted). 5) Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment). 6) Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor’s medical monitor."}
• {"criterion_text":"- Stroke, transient ischemic attack or seizure within 6 months prior to signing ICF"}
• {"criterion_text":"- Presence of the following cardiac conditions: a. New York Heart Association stage III or IV congestive heart failure (see Appendix ) b. Myocardial infarction or coronary artery bypass graft ≤6 months prior to enrollment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina) c. Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities d. History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration e. History of severe non-ischemic cardiomyopathy"}
• {"criterion_text":"- 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, such as: a. Uncontrolled diabetes b. Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy c. History of autoimmune disease with the exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing d. Gastrointestinal disease that may significantly alter the absorption of oral drugs e. Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status"}
• {"criterion_text":"- Any other issue that would impair the ability of the participant 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 participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments a. History of non-compliance with recommended medical treatments b. Unable or unwilling to undergo antithrombotic prophylactic treatment"}
• {"criterion_text":"- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the appropriate IBs and SmPCs)"}

Primary endpoints

• {"endpoint_text":"- MRD measured by NGS (sensitivity level of 10-6) and FDG PET-CT scan using the Deauville score and CR evaluated per IMWG 2016 response criteria after 6 cycles of talquetamab and 6 cycles of teclistamab consolidation therapy","definition_or_measurement_approach":"MRD measured by NGS with sensitivity level of 10^-6; FDG PET-CT scan assessed using the Deauville score; CR evaluated per IMWG 2016 response criteria after specified cycles of consolidation therapy."}

Secondary endpoints

• {"endpoint_text":"- MRD measured by NGS (sensitivity level of 10-6) and FDG PET-CT scan using the Deauville score and CR evaluated per IMWG 2016 response criteria after 6 cycles of Dara-VRd induction","definition_or_measurement_approach":"MRD measured by NGS (sensitivity 10^-6); FDG PET-CT using Deauville score; CR per IMWG 2016 response criteria after 6 cycles of Dara-VRd induction."}
• {"endpoint_text":"- Percentage of participants converting from positive MRD to negative MRD (sensitivity level of 10-6) after 6 cycles of talquetamab","definition_or_measurement_approach":"Conversion assessed by NGS MRD testing with sensitivity level 10^-6 after 6 cycles of talquetamab."}
• {"endpoint_text":"- Percentage of participants converting from positive MRD to negative MRD (sensitivity level of 10-6) after 6 cycles of teclistamab","definition_or_measurement_approach":"Conversion assessed by NGS MRD testing with sensitivity level 10^-6 after 6 cycles of teclistamab."}
• {"endpoint_text":"- Proportion of participants with persistent MRD negative disease at month 12 and 24 after completing treatment with teclistamab, by NGS (sensitivity level of 10-6), and FDG PET-CT scan","definition_or_measurement_approach":"Persistence measured by NGS MRD (sensitivity 10^-6) and FDG PET-CT at months 12 and 24 post-treatment."}
• {"endpoint_text":"- Overall Response Rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to next anti-myeloma treatment (TTNT)","definition_or_measurement_approach":""}
• {"endpoint_text":"- TEAEs according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE, Version 5.0)","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE Version 5.0."}
• {"endpoint_text":"- Incidence of participant-recorded side effects (during the treatment with talquetamab and teclistamab) Impact of treatment on (physical, social, cognitive, emotional, overall) quality of life","definition_or_measurement_approach":"Participant-recorded side effects and quality-of-life measures collected (questionnaires listed in documents e.g., QLQ-C30, PRO-CTCAE, FACT-Cog)."}
• {"endpoint_text":"- MRD status 100 days after starting of standard of care treatment","definition_or_measurement_approach":"MRD assessed by NGS (sensitivity level of 10^-6) 100 days after start of standard of care."}

Denmark

Earliest CTIS Part Ii Submission Date

01-03-2024

Latest Decision Or Authorization Date

12-09-2025

Processing Time Days

561

Number Of Sites

3

Number Of Participants

11

Estonia

Earliest CTIS Part Ii Submission Date

08-03-2024

Latest Decision Or Authorization Date

12-09-2025

Processing Time Days

554

Number Of Sites

1

Number Of Participants

9

Norway

Earliest CTIS Part Ii Submission Date

13-03-2024

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

547

Number Of Sites

3

Number Of Participants

30

Primary sponsor

Full Name

North Estonia Medical Centre Foundation

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Estonia

Third parties

• {"country":"Croatia","full_name":"Optimapharm d.o.o.","duties_or_roles":"1,12,5,6,8","organisation_type":"Pharmaceutical company"}