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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumours

Intervention / Treatment
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* Drug: EXS21546


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXS21546<br>EXS21546 Granule in Capsule for oral administration | Drug: EXS21546<br>* EXS21546 Granule in Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of EXS21546 in combination with nivolumab. | 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. | Through study completion, an average of 6 months | 
| Dose-limiting toxicities (DLTs) of EXS21546 in combination with nivolumab. | 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. | Through dose escalation completion, an average of 6 months | 
| Preliminary anti-tumoural activity of EXS21546 in combination with nivolumab. | Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. | Through study completion, an average of 6 months | 
| Treatment adherence of EXS21546 in combination with nivolumab. | Number of doses recorded in the treatment diary. | Through study completion, an average of 6 months | 
| Tolerability of EXS21546 in combination with nivolumab. | Frequency of dose interruptions, dose reductions and dose intensity achieved. | Through study completion, an average of 6 months |