A Modular, Multi-part, Multi-arm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD5769 Alone and in Combination with Anticancer Treatments in Patients with Solid Malignancies

Solid malignancies

Incidence, type and severity of treatment-emergent and treatment-related adverse events (AEs), Incidence and nature of DLTs

The MTD will be determined by the incidence of DLTs according to the MTD evaluation process., The RP2D will be determined based on the safety, tolerability, PK, PDc and preliminary efficacy data of GRWD5769. The RP2D will not exceed the MTD., Pharmacokinetic parameters to be evaluated (where possible) include (but are not limited to): • Trough concentrations • Maximum observed concentration (Cmax) • Time to Cmax (Tmax) • Trough concentrations • Area under the concentration-time curve (AUC0-t) • Half-life (t1/2) • Oral clearance (CL/F) • Absorption-dependent apparent volume of distribution in steady state (Vss/F), RECIST 1.1 or iRECIST defined tumour response, including the frequency, quality and durability of response per RECIST 1.1 or iRECIST criteria. Specific endpoints include (but are not limited to): o Tumour size Objective response rate (ORR) o Disease control rate (DCR) o Rate of participants with stable disease (stable disease rate [SDR]), defined as the proportion of participants with stable disease of at least 16 weeks per RECIST 1.1 or iRECIST o Time to response (TTR) - please see protocol., Change from baseline in disease-specific tumour markers (e.g. CA-125 for ovarian cancer, PSA for prostate cancer), The MBAD is defined as the dose that achieves one of the following: a. Average total daily plasma (Cssave) of 3899 ng/mL b. A partial or complete RECIST 1.1 or iRECIST assessed response in at least one participant c. A clinically significant reduction (in the opinion of the safety review committee [SRC]), compared to baseline, in a tumour specific marker measured in at least one participant

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France, Spain