TED18162 - Studio di fase 1, in aperto, condotto per la prima volta sull’uomo per valutare la sicurezza, l’attività antitumorale, la farmacocinetica e la farmacodinamica di SAR446523 per via sottocutanea, un anticorpo monoclonale anti-GPRC5D potenziato con ADCC in pazienti con mieloma multiplo recidivante/refrattario.

Studio Clinico

Patologia: Mieloma, Neoplasie ematologiche

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1,

Linee di trattamento: Terza/N linea

Criteri di inclusione: 

Participants are eligible to be included in the study only if all of the following criteria apply:

Age
01. Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent.

Type of participant and disease characteristics
02. Participants with a documented diagnosis of MM.
03. Participants with measurable disease defined as at least one the following:
    - Serum M-protein ≥1.0 g/dL and/or,
    - Urine M-protein ≥200 mg/24 hours and/or,
    - Serum FLC assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal
serum FLC ratio (<0.26 or >1.65).

Dose escalation (Part A)
04. Participants must have received at least 3 prior lines of antimyeloma therapy which must include a second or third generation immunomodulator (eg, lenalidomide, pomalidomide), PI (eg, bortezomib, carfilzomib, ixazomib), and anti-CD38 mAb (eg, isatuximab, daratumumab) administered with the same or different line.
AND
Must be either relapsed or refractory to the above therapies, or are intolerant to them, based up on the Investigator’s judgment.
Note: In Part A, prior exposure to anti-GPRC5D therapy and anti-BCMA therapy is allowed.
Please refer to Section 10.8 for country specific requirement for I 04.

Dose optimization (Part B)
05. Participants must have received at least 3 prior lines of antimyeloma therapy which must include a second or third generation immunomodulator (eg, lenalidomide, pomalidomide), PI (eg, bortezomib, carfilzomib, ixazomib), anti-CD38 mAb (eg, isatuximab,
daratumumab), and anti-BCMA (eg, teclistamab, elranatamab, idecabtagene vicleucel, ciltacabtagene autoleucel, belantamab mafodotin) administered with the same or different line.
AND
Must be either relapsed or refractory to the above therapies, or are intolerant to them, based up on the Investigator’s judgment.
Note: In Part B, prior exposure to anti-GPRC5D therapy is not allowed.

Sex, contraceptive/barrier method and pregnancy testing requirements/breastfeeding
06. All Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    a) Male participants
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 180 days after the last administration of study intervention:
- Refrain from donating or cryopreserving sperm
PLUS, either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on long-term and persistent basis) and agree to remain abstinent.
OR
- Must agree to use contraception/barrier as detailed below:
- A male condom and an additional highly effective contraceptive method as described in Section 10.4 when having sexual intercourse with a WOCBP who is not currently pregnant.
    b) Female participants
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
    - Is a WONCBP as defined in Section 10.4.
OR Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), (preferably) with low user dependency, as described in Section 10.4 during the study treatment period (to be effective before
starting the treatment) and for at least 120 days after the last administration of study treatment and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.
    - A WOCBP must have a negative serum or highly sensitive urine pregnancy test
(with a minimum sensitivity of 25 mIU/mL) as required by local regulations within 14 days before the first administration of study intervention and again within 24 hours of initiation of study treatment, see Section 8.3.5.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

Informed Consent
07. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Criteri di esclusione: 

Medical conditions
- 01. ECOG PS of 2 or greater.
- 02. Primary systemic and localized AL amyloidosis, active POEMS syndrome, active plasma cell leukemia at the time of screening.
- 03. Diagnosis of any other malignancy within 2 years prior to first IMP administration.
Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, in situ cervical cancer, superficial (pTis, Pta, or pT1) bladder cancer; papillary thyroid cancer, low-risk prostate cancer (ie, cT1-2a, Gleason score under 7, an prostate-specific antigen below 10 ng/mL), in situ breast cancer, or in situ carcinoma, local/locoregional GIST resected R0 are allowed.
- 04. Congestive heart failure (New York Heart Association) Grade ≥2; cardiomyopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension. Acute myocardial infarction within 6 months before the first IMP administration.
- 05. Clinically uncontrolled chronic or ongoing infectious disease requiring antibiotic, antiviral or antifungal treatment at the time of first dose or within 14 days before the first dose.
- 06. Presence of HBsAg (or HBcAb with positive DNA test result) at screening or within 3 months prior to first administration of study treatment.
- 07. Positive HCV Ab test result at screening or within 3 months prior to starting study treatment. NOTE: Participants with positive HCV Ab due to prior resolved disease can be enrolled, only if a confirmatory negative HCV RNA test is obtained.
- 08. Participants with known AIDS-related illness or known HIV disease requiring antiviral
treatment.

Prior/concomitant therapy
- 09. Prior treatment with anti-GPRC5D therapy (in Part B only).
- 10. Prior treatment with NK-cell engaging therapy (such as a mAb with ADCC as primary mechanism of action, eg, isatuximab, daratumumab) within 90 days of the first IMP administration.
- 11. Systemic antimyeloma treatment within 14 days before the first IMP administration.
- 12. Prior allogenic stem cell transplant with active GvHD (GvHD any grade and/or treatment with immunosuppressive drugs within 2 months prior to study entry).
- 13. Any major procedure such as plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy within 14 days before the initiation of the study treatment.
- 14. Ongoing AE of NCI CTCAE (version 5.0) Grade 2 or greater severity caused by any prior anticancer therapy (with exception of Grade 2 alopecia, Grade 2 peripheral neuropathy stable for 3 months).
- 15. Vaccination with a live vaccine 4 weeks before the first IMP administration.

Prior/concurrent clinical study experience
- 16. Participation in any other clinical study involving an investigational study treatment within 28 days or 5 half-lives of the study treatment, whichever is longer prior to first IMP administration.

Diagnostic assessments
- 17. Hemoglobin <8 g/dL.
Red blood cell transfusion within 7 days prior to screening hematological testing not allowed. Use of erythropoiesis stimulating agent is allowed.
- 18. Absolute neutrophil count <1000/μL (<1 × 109/L).
  No G-CSF within 7 days or pegylated G-CSF is permitted, respectively, before the screening hematological test.
- 19. Platelet <50 000/μL (<50 × 109/L).
Platelet transfusion is not allowed within 7 days before the screening hematological test.
- 20. Total bilirubin >1.5 × ULN. In participants with known Gilbert syndrome direct bilirubin should not be >3 × ULN.
- 21. AST/SGOT or ALT/SGPT >2.5 × ULN.
- 22. eGFR <30 mL/min/1.73 m2 using MDRD formula – see Section 10.2.1: Modification of diet in renal disease (MDRD) equation.
- 23. Grade 3 or 4 hypercalcemia (corrected serum calcium of >12.5 mg/dL; >3.1 mmol/L; ionized calcium >1.6 mmol/L; or requiring hospitalization) will not be eligible unless patients recover to Grade 2 or less under antihypercalcemia treatment.

Other exclusion criteria
- 24. Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
- 25. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
- 26. Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6).
- 27. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

Schema di trattamento: 

Participants will receive SAR446523 depending on DL on Day 1, 8, 15, and 22 of Cycle 1 (QW schedule) and on Day 1 and 15 thereafter (Q2W schedule).

Trattamento sperimentale: 

SAR446523

Trattamento di controllo: 

NA

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2024-511667-28

Data di inserimento: 19.02.2025

Promotore

Sanofi

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na