Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies

Redx Pharma

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumor; Cancer

Treatments: Drug: RXC004; Drug: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03447470

RXC004/0001

Details and patient eligibility

About

The purpose of this study is to determine the safety and tolerability of RXC004 as monotherapy and in combination with Nivolumab in patients with advanced malignancies. In order to define the doses and schedules for further clinical evaluation.

Full description

The study will consist of an ascending monotherapy dose, the doses are pre-defined.

The decision to escalate will be made upon the assessment of safety and tolerability data in the first cycle of treatment.

Module 1 will commence with a 3+3 dose escalation design up to a recommended Phase 2 monotherapy dose. Patients being monitored for dose limiting toxicities at each dose level.

Characterisation of the PK profile, MTD and/or recommended Phase 2 dose will be defined on the emerging data.

Module 2: RXC004 and Nivolumab - Follows a similar 3+3 dose escalation design using RXC004 plus Nivolumab. The MTD and/or Phase 2 dose will be defined based on the PK profile, emerging safety and the appearance of any dose limiting toxicities.

Module 3: Intermittent dose schedules of RXC004 will be investigated. The intermittent schedules will utilize the module 1 dose which was shown to be safe and tolerated when used continuously. Characterisation of the PK profile; Wnt pathway inhibition; incidence/severity of Wnt pathway related AEs and anti-tumor activity will be evaluated at 2 different dosing schedules.

Enrollment: 46 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

(Summarized due to limitation of characters)

Inclusion Criteria:

• Written informed consent
• Aged at least 18 years
• Histological or cytological confirmation of advanced malignancy not considered to be appropriate for further conventional treatment
• Patients must use adequate contraception measures for the duration of the study and for 6 months after the study
• Patients must have adequate organ functions
• Ability to swallow and retain oral medication

Exclusion Criteria:

• Prior treatment with a compound of the same mechanism of action as RXC004
• No other anti-cancer therapy or investigational product throughout the study
• Patients with persistent grade 2 or higher diarrhoea
• Patients at high risk of bone fractures
• QTc prolongation
• Known uncontrolled intercurrent illness
• Known severe allergies to any active or inactive ingredients

In addition for Module 2

• Patients with any contraindication/hypersensitivity to Nivolumab of excipients
• Patients with active or prior documented autoimmune of inflammatory disorders within the past 5 years
• Patients with active infections, including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus
• Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study treatment
• Patients with body weight <40kg
• Patients with a history of allogeneic organ transplant or active primary immunodeficiency

In addition to Module 3

Patients with Wnt ligand-dependent solid tumours, defined as:

• Biliary tract cancers
• Thymus cancers (thymic and thymoma WHO classification)
• Any solid tumour with documented aberration in RNF43 and/or RSPO from central pre-screening or from a recognised panel approved by the Sponsor
• Patients willing to have mandatory skin biopsies at baseline and on one occasion while on study treatment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

46 participants in 3 patient groups

Monotherapy RXC004 - Module 1

Experimental group

Description:

Patients will be given RXC004 at a specified dose level and reviewed for Dose Limiting Toxicities. Once the DLT period is complete RXC004 will be given at a higher dose until MTD is reached.

Treatment:

Drug: RXC004

Combination RXC004 plus Nivolumab - Module 2

Experimental group

Description:

Patients will be given RXC004 at specific doses in combination with a standard dose of Nivolumab and reviewed for Dose Limiting Toxicities. Once the DLT period is complete, RXC004 will be given at a higher dose until MTD is reached.

Treatment:

Drug: Nivolumab

Drug: RXC004

Intermittent schedules of monotherapy RXC004 - Module 3

Experimental group

Description:

Patients will be given RXC004 at specific doses. One group will be treated for 4 days, followed by 3 days off; repeated weekly for 21 days. A second group will be treated for 2 weeks at the same dose, followed by 1 week off for 21 days.

Treatment:

Drug: RXC004