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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-18

Study Completion Date

2023-09-29

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Cancer Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Module 1 monotherapy Dose escalation in those patients with advanced solid tumors while being monitored for safety and dose-limiting toxicity. This module will provide information on dosing and schedules for further module(s).

Module 2 will commence by enrolling patients with advanced solid tumors into a monotherapy dose escalation, in combination with a fixed dose of nivolumab (a known anti-cancer treatment). This module will provide information and safety and tolerability of the study drug or in combination with the anti-cancer treatment.

Module 3 will investigate the pharmacokinetic, Wnt pathway inhibition, incidence/severity of Wnt pathway related adverse events and anti-tumour activity of RXC004 when given at 2 different intermittent dosing schedules in selected patients with Wnt ligand dependent advanced tumours.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open label design

Study Groups

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Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg)

Patients were given 0.5 mg RXC004 and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 2 Arm 1 - RXC004 (1.0 mg) plus Nivolumab

Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1

Module 3 - Intermittent schedules of monotherapy RXC004

Patients were given 2.0 mg RXC004. The patients were treated for 2 weeks at the same dose, followed by 1 week off for a 21 day cycle.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg)

Patients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg)

Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg)

Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg)

Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg)

Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Module 2 Arm 2 - RXC004 (1.5 mg) plus Nivolumab

Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab

Intervention Type DRUG

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1

Interventions

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RXC004

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Intervention Type DRUG

Nivolumab

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1

Intervention Type DRUG

Eligibility Criteria

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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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No