64007957MMY1008 - MajesTEC-10 - A Phase 1 Randomized, Open-Label Pharmacokinetic Comparability Study Comparing Pre- and Post-change Teclistamab in Participants with Relapsed/Refractory Multiple Myeloma.

Studio Clinico

Patologia: Mieloma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: 1,

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

Each potential participant must satisfy all of the following criteria to be enrolled in the study:Each potential participant must satisfy all of the following criteria to be enrolled in the study:

1. ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, if older) at the time of informed consent.
2. Documented diagnosis of multiple myeloma as defined by the criteria below:
    • Multiple myeloma diagnosis according to IMWG diagnostic criteria (Appendix 4).
    • Measurable disease at screening as defined by any of the following:
        o Serum M-protein level ≥0.5 g/dL (central laboratory); or
        o Urine M-protein level ≥200 mg/24 hours (central laboratory); or
        o Serum immunoglobulin free light chain ≥10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
NOTE: All attempts should be made to determine eligibility of the participant based on the central laboratory results of screening blood and urine M-protein measurements. In exceptional circumstances and after discussion with and written approval by the Sponsor, the local laboratory results of blood and urine M-protein measurements may be used to determine initial eligibility.
3. Relapsed or refractory disease as defined below:
    • Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease by IMWG criteria >60 days after cessation of treatment.
    • Refractory disease is defined as failure to achieve a response or confirmed progressive disease by IMWG criteria during previous treatment or ≤60 days after cessation of treatment.
4. Received 1 to 3 prior lines of antimyeloma therapy, including a minimum of 2 consecutive cycles each of a PI, lenalidomide, and an anti-CD38 monoclonal antibody (or minimum of 6 doses if anti-CD38 monoclonal antibody was only part of a maintenance regimen) in any prior line.NOTE: A single line of therapy may consist of 1 or more agents and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonates, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy (Appendix 17).
5. Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator’s determination of response by IMWG criteria.
6. Have an ECOG performance status score of 0 to 2 (Section 8.3.9, Appendix 5).
7. Have clinical laboratory values meeting the following criteria.
    • Hemoglobin g/dL ( 5 mmol/L); without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted.
    • Platelets ×109/L in participants in whom <50% of bone marrow nucleated cells are plasma cells; 50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells. For all applies without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test.
    • 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).
    • AST and ALT ≤2.5×ULN.• eGFR ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation (Appendix 6) or creatine clearance measured by a 24-hour urine collection.
    • Total bilirubin Total bilirubin ≤2×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case if total bilirubin is >2×ULN, then direct bilirubin ≤1.5×ULN is required).
    • Serum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L; see Appendix 7).
8. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
9. A female participant must be (as defined in Appendix 8):
    • Not of childbearing potential, or
    • Of childbearing potential and practicing at least 1 highly effective method of contraception (see Appendix 8)
NOTE: Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy (Appendix 8).
NOTE: Participant must agree to continue from time of signing the ICF until 6 months after the last dose of study treatment.
NOTE: If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with (b) as described above. If a participant’s reproductive status is questionable, additional evaluation should be considered.
NOTE: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
10. 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 a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anticancer treatments may impair fertility.
11. 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 3 months 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 (see Appendix 8).
NOTE: If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception.
12. A male participant must agree not to donate sperm for the purpose of reproduction during the study and a period of 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility.
13. Must sign an ICF (or their legally acceptable representative must sign in accordance with local legislation) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
14. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 5.3).

Criteri di esclusione: 

Any potential participant who meets any of the following criteria will be excluded from'Any potential participant who meets any of the following criteria will be excluded fromparticipating in the study:

1. Received any bispecific antibody and/or CAR-T cell therapy
2. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator’s Brochure and Addenda).
3. Modified per Amendment 1
3.1 Received the following prior antimyeloma therapy, within the specified time frame prior to randomization:
    a. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥5 half-lives, whichever is less
    b. Investigational vaccine within 4 weeks
    c. Monoclonal antibody therapy within 21 days
    d. Cytotoxic therapy within 21 dayse. PI therapy within 14 daysf. IMiD agent therapy within 14 daysg. Radiotherapy within 14 days or focal radiation within 7 daysh. Plasmapheresis within 28 days
4. Received a maximum cumulative dose of corticosteroids of ≥140 mg of prednisone or equivalent within 14 days prior to randomization (see Appendix 10)
5. Stem cell transplant:
    a. An allogeneic stem cell transplant within 6 months before randomization. Participants who received an allogeneic transplant must be off all immunosuppressive medicationsfor ≥42 days without signs of graft‑versus‑host disease before randomization.
    b. An autologous stem cell transplant within 12 weeks prior to randomization.
6. Received a live, attenuated vaccine within 4 weeks before the first dose of study drug.Non-live or non-replicating vaccines authorized for emergency use (eg, COVID-19; see Appendix 19) by local health authorities are allowed.
7. CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology may be required.
8. Plasma cell leukemia, smoldering multiple myeloma, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skinchanges), or primary amyloid light chain amyloidosis.
9. Any of the following:
    a. Any ongoing myelodysplastic syndrome or B cell malignancy (other than multiple myeloma).
    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 malignanciestreated within the last 24 months that are considered cured:
    1) Non-muscle invasive bladder cancer (solitary Ta-PUNLMP 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.
NOTE: In the event of any questions, consult with the Sponsor’s medical monitor prior to enrolling a participant.
10. Stroke, transient ischemic attack, or seizure within 6 months prior to randomization.
11. Presence of the following cardiac conditions.
    a. New York Heart Association stage III or IV congestive heart failure (Appendix 11)
    b. Myocardial infarction, unstable angina, or coronary artery bypass graft ≤6 months prior to randomization
    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
12. 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.
13. Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
14. Participant had major surgery or had significant traumatic injury within 2 weeks prior to randomization, or will not have fully recovered from surgery, or has major surgery plannedduring the time the participant is expected to be treated in the study.
NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is aquestion whether a procedure is considered a major surgery, the investigator must consult with the appropriate Sponsor representative and resolve any issues before enrolling a participant inthe study.
15. 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 forparticipating in this study, such as:
    a. Acute diffuse infiltrative pulmonary disease
    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 thyroid disease that is currently euthyroid based on clinical symptoms and laboratory testing
    d. Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status
    e. History of noncompliance with recommended medical treatments
    f. 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
16. Seropositive for hepatitis B: defined by a positive test for HBsAg. Participants with resolved infection (ie, participants who are HBsAg negative with antibodies to total anti-HBc with or without the presence of anti-HBs) must be screened using RT-PCR measurement of HBV-DNA levels. Participants with a known history of HBV infection must be screened using RT-PCR measurement of HBV-DNA levels irrespective of serological results. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV-DNA by RT-PCR (see Appendix 9).
17. 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 12 weeks following the completion of therapy, the participant is eligible for the study.
18. Human immunodeficiency virus-positive with 1 or more of the following:
    a. History of AIDS-defining conditions
    b. CD4 count <350 cells/mm3
    c. Detectable viral load during screening or within 6 months prior to screening
    d. Not receiving highly active antiretroviral therapy
    e. Had a change in antiretroviral therapy within 6 months of the start of screening
    f. Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Sponsor.

Schema di trattamento: 

Si tratta di uno studio di fase 1, randomizzato (in rapporto 1:1), in aperto, multicentrico volto a valutare la comparabilità della PK tra teclistamab ottenuto dal processo di produzione precedente alla modifica (Braccio A) rispetto al processo di produzione successivo alla modifica (Braccio B). Il coinvolgimento dei partecipanti includerà un Periodo di screening (fino a 28 giorni), un Periodo di trattamento e un Periodo di follow-up.
Teclistamab sarà somministrato in cicli di 28 giorni in entrambi i bracci:
- Ciclo 1 Giorno 1: 1a dose incrementale 0,06 mg/kg
- Ciclo 1 Giorno 4: 2a dose incrementale 0,3 mg/kg
- Ciclo 1 Giorno 7, 14, 21: dose trattamento 1,5 mg/kg
- Ciclo 2, nei Giorno 1, 8, 15, 22: dose trattamento 1,5 mg/kg
- Ciclo da 3 a 6, nei Giorni 1 e 15: dose trattamento 3 mg/kg
- Da Ciclo 7, nei Giorni 1: dose trattamento 3 mg/kg.

Trattamento sperimentale: 

Teclistamab prodotto con nuovo processo produttivo.

Trattamento di controllo: 

Teclistamab prodotto con vecchio processo produttivo.

Obiettivi primari dello studio: 

L’obiettivo primario di questo studio è valutare la comparabilità della PK di teclistamab in monoterapia utilizzando teclistamab dal processo di produzione precedente alla modifica con quello del processo di produzione successivo alla modifica.

Obiettivi secondari dello studio: 

Gli obiettivi secondari principali sono la valutazione di efficacia, sicurezza e immunogenicità.

Note generali: 

Data inizio arruolamento: giugno/luglio 2024
Data fine arruolamento: dicembre 2024.

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2023-508426-10 - 2023-508426-10-00

Data di inserimento: 30.09.2024

Promotore

Janssen Research & Development, LLC

Principal Investigator ITALIA

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: nd