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Study to Assess EXS21546 in Combination in Patients With Advanced Solid Tumours

Phase 1
Terminated
Conditions
Advanced Solid Tumours
Interventions
Registration Number
NCT05920408
Lead Sponsor
Exscientia AI Limited
Brief Summary

A phase 1B/2A study to assess the safety, tolerability, pharmacokinetic and anti-tumoral activity of EXS21546 in combination with a PD-1 inhibitor in patients with advanced solid tumours.

Detailed Description

A phase 1B/2A study to assess the safety, tolerability, pharmacokinetic and anti-tumoral activity of EXS21546 in combination with a PD-1 inhibitor, nivolumab, in patients with advanced solid tumours, non small cell lung cancer and renal cell carcinoma.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
Inclusion Criteria
  • Aged ≥ 18 years at time of informed consent.
  • Previous histologically confirmed diagnosis of RCC or NSCLC having received previously checkpoint inhibitors as part of a SoC regimen.
  • Consent to mandatory paired tumour biopsies of at least one tumour site accessible for repeat biopsies. Planned sites for tumour biopsies must not have been previously irradiated and could be a target lesion of >2 cm diameter according to RECIST v1.1 and must be approved on a case-by-case basis by the Sponsor.
  • Measurable disease as per RECIST v1.1 and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI).
Exclusion Criteria
  • Any anti-tumour therapy, including investigational therapies, within 4 weeks prior to the first dose of EXS21546.
  • Unresolved or unstable serious toxic side-effects of prior chemotherapy or radiotherapy, i.e., ≥ Grade 2 per CTCAE v5.0.
  • Concurrent other malignancy that could interfere with response evaluation.
  • Symptomatic central nervous system (CNS) malignancy or metastases. Screening of symptomatic participants without history of CNS metastases is not required. Participants with asymptomatic CNS lesions should have completed standard therapy for their CNS lesions 60 days prior to study enrolment.
  • History of interstitial lung disease and/or prior immunotherapy-related pneumonitis.
  • Patients who have had or are scheduled to have major surgery < 28 days prior to the first dose of study drug.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
EXS21546EXS21546EXS21546 Granule in Capsule for oral administration
Primary Outcome Measures
NameTimeMethod
Safety of EXS21546 in combination with nivolumab.Through study completion, an average of 6 months

Incidence of treatment-emergent adverse events (TEAEs) and SAEs characterised by type, incidence, severity (graded by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0), seriousness, timing and relationship to EXS21546 dosing.

Dose-limiting toxicities (DLTs) of EXS21546 in combination with nivolumab.Through dose escalation completion, an average of 6 months

Incidence of dose limiting toxicities (DLTs) during Cycle 1 (initial 28 days) of treatment with escalating doses of EXS21546 in combination with an approved dose of nivolumab.

Preliminary anti-tumoural activity of EXS21546 in combination with nivolumab.Through study completion, an average of 6 months

Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

Treatment adherence of EXS21546 in combination with nivolumab.Through study completion, an average of 6 months

Number of doses recorded in the treatment diary.

Tolerability of EXS21546 in combination with nivolumab.Through study completion, an average of 6 months

Frequency of dose interruptions, dose reductions and dose intensity achieved.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (5)

CHU Mont-Godinne

🇧🇪

Namur, Belgium

Institute Jules Bordet

🇧🇪

Brussels, Belgium

Centre Eugene Marquis

🇫🇷

Rennes, France

Institut Bergonie

🇫🇷

Bordeaux, France

Centre GF Leclerc

🇫🇷

Dijon, France

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