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Innocuité et efficacité préliminaire du SA53-OS chez les patients atteints de tumeurs solides localement avancées ou métastatiques

5 novembre 2026 mis à jour par: Lamassu Bio Inc

Une étude ouverte de phase 1/2a sur l'innocuité, la tolérance, la pharmacocinétique et l'efficacité préliminaire du SA53-OS, un inhibiteur de MDM2, chez des patients atteints de tumeurs solides p53 de type sauvage localement avancées ou métastatiques

The objective of this study is to assess the safety, efficacy, and pharmacokinetics of SA53-OS in adult participants with refractory solid tumors.

The study is comprised of 2 parts: Part 1 called dose escalation, and Part 2a called dose expansion. This study starts with Part 1 where participants who are diagnosed with advanced or metastatic solid tumor cancers receive different doses of SA53-OS (starting with the lowest dose) to find the maximum tolerated dose (MTD) of SA53-OS. Once the MTD of SA53-OS is known, the study continues to Part 2a where participants who are diagnosed with dedifferentiated liposarcoma (DD LPS) or other solid tumor cancers will receive SA53-OS at the MTD.

The study drug, SA53-OS, will be administered for 3 consecutive days every 3 weeks as an oral solution for up to 2 years.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

This is a phase 1/2a, open-label, dose escalation study conducted in adult participants with p53 wild-type refractory solid tumors. The study will assess the safety, efficacy, and pharmacokinetics of SA53-OS a novel MDM2 inhibitor capable of selective activation of p53. This enables the p53 tumor suppressor protein to selectively facilitate tumor cell death and growth inhibition.

The study drug, SA53-OS, will be administered for 3 consecutive days every 3 weeks as an oral solution. Phase 1 will consist of a dose escalation study to establish a candidate recommended phase 2 dose (RP2D). Phase 2a will enroll 2 expansion cohorts to establish any preliminary efficacy of SA53-OS in participants with dedifferentiated liposarcoma (DD LPS) with MDM2 amplifications and other p53 wild-type solid tumors as a single agent.

Phase 1 dose escalation:

Escalating doses of SA53-OS will be provided to participants with p53 wild-type refractory solid tumors to determine the RP2D. The MTD is the highest dose of a drug or treatment that does not cause unacceptable side effects in the first cycle. The RP2D considers all available safety, pharmacokinetics, and efficacy data including, the frequency, severity, and manageability of toxicities occurring after Cycle 1.

Phase 1 of the study will start with dose escalation by 2-fold (i.e., 2x preceding dose level) in cohorts of a single participant until Grade 2 or greater toxicity is observed.

When a single Grade 2 or higher toxicity is observed, 3+3 multi-participant cohorts will be treated at the dose in which the Grade 2 or higher toxicity was observed by enrolling another 2 participants at this dose. The 3+3 multi-participant cohorts will follow the standard 3+3 paradigm based on occurrence of any DLT with 50% dose escalation until the MTD is identified.

Phase 2a dose expansion:

The purpose of Phase 2a of the study is to describe any preliminary evidence of efficacy from SA53-OS monotherapy in participants with DD LPS or other p53 wild-type or MDM2 amplified solid tumors. Phase 2a will also be used to confirm the safety and tolerability of the candidate RP2D of SA53-OS determined in Phase 1 of the study, to further describe the toxicity and pharmacokinetics profiles of SA53-OS, and to assess potential biomarkers of sensitivity resistance, and toxicity.

Participants will continue to receive study treatment until either: 1) disease progression; 2) occurrence of unacceptable treatment-related toxicity as per participant or Investigator discretion; 3) the maximum of 2 years of treatment has been reached; or 4) other reason(s) for study treatment discontinuation. In the case of complete response, treatment should be continued for at least 6 months if no other stopping criteria are met, and further treatment can be recommended at the investigator's discretion.

Type d'étude

Interventionnel

Inscription (Estimé)

55

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • États-Unis
    • Ohio
      • Canton, Ohio, États-Unis, 44718
        • Recrutement
        • Gabrail Cancer Center
        • Chercheur principal:
          • Nashat Gabrail, MD
        • Contact:
      • Cleveland, Ohio, États-Unis, 44106
        • Recrutement
        • University Hospitals Cleveland Medical Center
        • Chercheur principal:
          • Afshin Dowlati, MD
        • Contact:
        • Contact:
      • Cleveland, Ohio, États-Unis, 44195
        • Recrutement
        • Cleveland Clinic Taussig Cancer Institute
        • Chercheur principal:
          • James Wooley
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Tumor characteristics of participants in Phase 1

    1. Histologically and/or cytologically confirmed diagnosis of advanced or metastatic solid tumor and/or non-Hodgkin lymphoma excluding primary central nervous system malignancy for which no standard effective treatment exists or where that treatment was declined. Participants with non-Hodgkin lymphoma should have failed ≥ 2 prior lines of systemic therapy prior enrollment.
    2. Tumor p53 wild-type.

  • Tumor characteristics of participants in Phase 2a

    1. Cohort A: Tumor p53 wild-type with histologically confirmed diagnosis of advanced or metastatic DD LPS (and MDM2 amplification); OR Cohort B: Tumor p53 wild-type in other solid tumor.
    2. Measurable disease by RECIST 1.1.

  • 18 years old or older.

  • Resolution of clinically relevant toxicity-related to prior anticancer therapies prior to receipt of study treatment to Grade 1 or less.

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • Participants of childbearing/reproductive potential must agree to use adequate birth control measures during the course of the trial and for at least 3 months after discontinuing study treatment.

Exclusion Criteria:

  • Anticipated need for major surgery and/or localized palliative radiation within the next 6 weeks
  • Active, untreated central nervous system metastases. Participants with brain metastases identified at Screening may be rescreened after the lesion(s) have been appropriately treated; participants with treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment, and off corticosteroids for at least 2 weeks before start of study treatment, and treated lesions should demonstrate no new growth on the re-screening scan.
  • Known HIV infection or active hepatitis B or C infection.
  • Thrombotic event requiring active and ongoing anticoagulation within the last 6 months prior to study treatment.
  • Myocardial infarction within the last 6 months prior to study treatment.
  • Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure New York Heart Association (NYHA) Class III or IV related to primary cardiac disease, uncontrolled ischemic or severe vascular heart disease.
  • A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  • Known bleeding disorder (e.g., hemophilia, von Willebrand disease).
  • Conditions that may predispose to major bleeding (e.g., active GI ulcers, upper or lower GI bleedings in the last 6 months, significant hemoptysis in the last 6 months, tumor invasion of major vessels, etc.). Conditions that have been treated may be allowed if resolution of the risk is documented.
  • Use or indication for full dose anticoagulation or anti-platelet therapy including low dose aspirin.
  • Women who are pregnant or lactating.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Phase 1

Dose escalation phase
Médicament: SA53-OS (phase 1)

Dose escalation phase in which participants receive SA53-OS on 3 consecutive days every 3 weeks for a maximum of 2 years. Single participant cohorts will be enrolled until a Grade 2 or greater toxicity is observed and then 3+3 multi-participant cohorts will be enrolled until the MTD is identified.
Expérimental: Phase 2

Cohort A: DDLPS (MDM2 amplified and p53 wild-type) Cohort B: other p53 wild-type solid tumors
Médicament: SA53-OS (phase 2)

Dose expansion phase in which participants receive SA53-OS on 3 consecutive days every 3 weeks for a maximum of 2 years at the MTD identified in phase 1.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Phase 1: Incidence of DLT
Délai: 21 days

Incidence of DLT in Cycle 1 (Day 1 to 21)
21 days
Phase 1 and 2: Adverse events
Délai: Approximately 2 years

Frequency of adverse events
Approximately 2 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Phase 1: Peak plasma concentration
Délai: Day 4

Determine the pharmacokinetic profile of SA53-OS (Cmax)
Day 4
Phase 1: Area under the plasma concentration versus time curve between 0 and 24 hours
Délai: Day 4

Determine the pharmacokinetic profile of SA53-OS (AUC0-24)
Day 4
Phase 1: Half-life
Délai: Day 4

Determine the pharmacokinetic profile of SA53-OS (T1/2)
Day 4
Phase 2: Objective response rate (ORR)
Délai: Approximately 2 years

Participants achieving ORR defined as complete response (CR) rate plus partial response (PR) rate.

CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Approximately 2 years
Phase 2: Progression free survival (PFS)
Délai: Approximately 2 years

Participants not meeting the definition for progressive disease
Approximately 2 years
Phase 2: Overall survival
Délai: Approximately 2 years

To evaluate overall survival
Approximately 2 years
Phase 2: Duration of response
Délai: Approximately 2 years

Duration of response will be evaluated in responders
Approximately 2 years
Phase 2: Complete response rate
Délai: Approximately 2 years

Participants achieving CR defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Approximately 2 years
Phase 2: Stable disease rate
Délai: Approximately 2 years

Participants achieving stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Approximately 2 years
Phase 2: Disease control rate
Délai: Approximately 2 years

Participants achieving CR + PR + stable disease
Approximately 2 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Lamassu Bio Inc

Les enquêteurs

  • Directeur d'études: Gabi Hanna, MD, Lamassu Bio

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

16 juin 2025

Achèvement primaire (Estimé)

1 juillet 2031

Achèvement de l'étude (Estimé)

1 août 2031

Dates d'inscription aux études

Première soumission

15 août 2024

Première soumission répondant aux critères de contrôle qualité

27 août 2024

Première publication (Réel)

29 août 2024

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

5 novembre 2026

Dernière vérification

1 novembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • LB-SA53-101

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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