A First-in-Human Study Investigating BG-85738 Alone or in Combination With Other Antitumor Agents in Patients With Advanced or Metastatic Solid Tumors With Rat Sarcoma Virus (RAS) Mutations
A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-85738, Alone or in Combination With Other Antitumor Agents, in Patients With Advanced or Metastatic Solid Tumors With RAS Mutations
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
A solid tumor is an abnormal mass of tissue caused by the uncontrolled growth of cells which can develop in organs, bones, or soft tissues. An advanced or metastatic solid tumor is a cancer that has either grown into nearby tissues ("advanced") or spread to distant parts of the body ("metastatic").
Many types of solid cancers have a change (mutation) in a gene called RAS gene. In normal cells, RAS proteins work by controlling when cells grow and divide. RAS mutations in cancer cells might lead to hyperactivation of the RAS proteins, which can result in continuous and uncontrolled growth of cancer cells. BG-85738 is a new experimental medicine that has been designed to block RAS proteins that are hyperactive.
The purpose of this study is to test whether BG-85738 is safe and if it can help to treat adults with advanced or metastatic solid tumors with a RAS mutation. This study has two parts, one called dose escalation, and one called safety expansion. During the dose escalation part, the study doctors will test different doses of the study drug[s] to find the recommended dose that people can take without having serious side effects.
During the dose expansion part, the study doctors will test the study drug in a larger number of people using the dose[s] identified from dose escalation.
The study will enroll patients at multiple centers worldwide who have been diagnosed with an advanced solid tumor that has a RAS gene mutation. The overall time to participate in this study is approximately 13 to 24 months. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and for tumor and imaging tests.
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Study Director
- Numéro de téléphone: 877-828-5568
- E-mail: clinicaltrials@beonemed.com
Lieux d'étude
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Queensland
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South Brisbane, Queensland, Australie, QLD 4101
- Recrutement
- ICON Cancer Centre South Brisbane
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Victoria
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Malvern, Victoria, Australie, VIC 3144
- Recrutement
- Cabrini Hospital Malvern
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
Inclusion Criteria:
Participants are eligible to be included in the study only if they meet all the following criteria:
- Participants must sign the informed consent form and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Participants must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older), at the time of signing the ICF.
- Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors and meet study part and cohort-specific criteria
- Participants must have evidence of a RAS mutation defined as a nonsynonymous mutation in Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), or Harvey rat sarcoma viral oncogene homolog (HRAS) at codons 12, 13, or 61 (G12, G13, or Q61), based on testing of either tumor tissue or liquid biopsy (blood or plasma) as determined by the local laboratory
Exclusion Criteria:
Participants are excluded from the study if they meet any of the following criteria:
- Participants who have prior RAS-targeted therapy, including, but not limited to, KRAS mutation-specific inhibitors (with the exception of participants with NSCLC and colorectal cancer who received a G12C inhibitor), pan-KRAS inhibitors, and pan-RAS inhibitors.
- Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of study treatment.
- Participants who are unable to comply with the requirements of the protocol.
- Participants with active leptomeningeal disease or uncontrolled, untreated brain metastases
- Participants with any malignancy ≤ 3 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
- Participants with active hepatitis C.
- Participants with medical history of untreated Human Immunodeficiency Virus infection.
Note: Other protocol defined criteria may apply.
Plan d'étude
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 |
|---|---|
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Expérimental: Phase 1a: Part A- Monotherapy Dose escalation and safety
Ascending dose levels of BG-85738 will be evaluated as monotherapy in participants with advanced or metastatic solid tumors with RAS mutations.
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Administered orally
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Expérimental: Phase 1a: Part B - Combination therapy Dose escalation
Sequential dose levels of BG-85738, selected based on Part A data, will be evaluated in combination with tislelizumab or in combination with cetuximab.
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Administré par voie intraveineuse
Administré par voie intraveineuse
Administered orally
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Expérimental: Phase 1b: Part C- Monotherapy dose expansion
Participants with selected tumor types will receive BG-85738 monotherapy at the RDFE(s) identified in Phase 1a Part A.
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Administered orally
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Expérimental: Phase 1b: Part D - Combination therapy dose expansion
Participants with select tumor types will receive BG-85738 in combination with tislelizumab or in combination with cetuximab at the RDFE(s) identified in Phase 1a Part B
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Administré par voie intraveineuse
Administré par voie intraveineuse
Administered orally
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Phase 1a (Part A and Part B): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Délai: From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
|
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose,
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From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
|
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Phase 1a (Parts A and B): Number of Participants with Dose Limiting Toxicity (DLT)
Délai: Up to approximately 1 month
|
Up to approximately 1 month
|
|
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Phase 1a (Parts A and B): Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-85738 as monotherapy or in combination with other antitumor agents
Délai: Up to approximately 1 month
|
MTD is defined as the highest dose level with the target DLT closest but not exceeding 0.33. MAD is defined as the maximum administered dose and it is used when MTD is not reached. |
Up to approximately 1 month
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Phase 1a: Recommended Dose for Expansion (RDFE) of BG-85738
Délai: Up to approximately 1 month
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Up to approximately 1 month
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|
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Part 1b (Parts C and D): Overall Response Rate (ORR)
Délai: Up to approximately 24 months
|
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).
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Up to approximately 24 months
|
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Phase 1b Dose Expansion: Recommended Phase 2 dose (RP2D) of BG-85738
Délai: Up to approximately 24 months
|
Up to approximately 24 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Phase 1a (Part A and Part B): Terminal Half Life (t1/2) of BG-85738
Délai: Up to approximately 2 months
|
Up to approximately 2 months
|
|
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Phase 1a (Part A and Part B): Area Under the Plasma Concentration-Time Curve (AUC) of BG-85738
Délai: Up to approximately 2 months
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Up to approximately 2 months
|
|
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Phase 1a (Part A and Part B): Minimum Observed Serum Concentration (Ctrough) of BG-85738
Délai: Up to approximately 2 months
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Up to approximately 2 months
|
|
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Phase 1a (Part A and Part B): Maximum Observed Plasma Concentration (Cmax) of BG-85738
Délai: Up to approximately 2 months
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Up to approximately 2 months
|
|
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Phase 1a (Part A and Part B): Overall Response Rate (ORR)
Délai: Up to approximately 24 months
|
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).
|
Up to approximately 24 months
|
|
Phase 1b (Parts C and D): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Délai: From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
|
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose,
|
From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
|
|
Phase 1b (Part C and D): Duration of response (DOR)
Délai: Up to approximately 24 months
|
DOR is defined as the time from the first determination of an overall response until the first documentation of progression or death, whichever comes first.
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Up to approximately 24 months
|
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Phase 1b (Part C and D): Disease control rate (DCR)
Délai: Up to approximately 24 months
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DCR is defined as the percentage of participants with best of response of a CR, PR, and stable disease.
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Up to approximately 24 months
|
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Phase 1b (Part C and D): Time to response (TTR)
Délai: Up to approximately 24 months
|
TTR is defined as the time from date of the first dose of study treatment to the first overall response.
|
Up to approximately 24 months
|
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Phase 1b (Part C and D): Progression-free survival (PFS) as assessed by the investigator
Délai: Up to approximately 24 months
|
PFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease or death, whichever occurs first, as assessed by the investigator per RECIST v1.1
|
Up to approximately 24 months
|
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Phase 1b (Part C): Intracranial Objective Response Rate (iORR)
Délai: Up to approximately 24 months
|
Intracranial objective response rate is defined as the percentage of patients with a best overall Intracranial response of CR or PR according to modified (m)RECIST v1.1 per Investigator assessment.
|
Up to approximately 24 months
|
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Phase 1b (Part C): Intracranial Duration of Response (iDOR)
Délai: Up to approximately 24 months
|
iDOR is defined as the time from the first determination of an overall intracranial response until the first documentation of progression or death, whichever comes first, with intracranial assessments by the investigator via modified RECIST v1.1 adapted for brain metastases.
|
Up to approximately 24 months
|
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Phase 1b (Part C): Intracranial Progression-free survival (iPFS) as determined from tumor assessments by the investigator
Délai: Up to approximately 24 months
|
iPFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease or death, whichever occurs first.
PFS is determined from tumor assessments by the investigator per a modified RECIST v1.1 adapted for brain metastases
|
Up to approximately 24 months
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Study Director, BeOne Medicine
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Tumeurs
- Processus néoplasiques
- Conditions pathologiques, signes et symptômes
- Métastase néoplasmique
- Acides aminés, peptides et protéines
- Protéines
- Anticorps, monoclonal, humanisé
- Anticorps, monoclonal
- Anticorps
- Immunoglobulines
- Immunoprotéines
- Protéines sanguines
- Globulines sériques
- Globulines
- Cétuximab
- tislelizumab
Autres numéros d'identification d'étude
- BG-85738-101
- 2026-526560-20-00 (Ctis)
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
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BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.
Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
Délai de partage IPD
Critères d'accès au partage IPD
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
- RSE
Informations sur les médicaments et les dispositifs, documents d'étude
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