The NOX66 clinical development program has two broad objectives - to develop NOX66 as:
- An enhancer of radiotherapy (DARRT program).
- An enhancer of cytotoxic chemotherapy (CEP program).
RADIOTHERAPY - DARRT program
The Direct and Abscopal Response to RadioTherapy (DARRT) program is the Company’s primary clinical program. The aim of this program is to determine the ability and safety of NOX66 in enhancing the effect of radiation across a range of tumour types. Radiation can be delivered externally (“External Beam Radiotherapy”) or internally, by targeted therapies. Noxopharm plans to investigate NOX66 with both forms of radiotherapy.
The aim of the DARRT program is to see if NOX66 improves the effect of radiotherapy on tumours directly exposed to radiation and whether the enhancement of effect can stimulate an additional indirect effect, extending to tumours outside of the field of irradiation, providing an “abscopal” effect against the cancer.
A. NOX66 plus external radiotherapy:
One Phase 1b study is currently open for recruitment (DARRT-1). The aim of this study is to identify the appropriate dose of NOX66 to use in all future trials and to confirm the safety of NOX66 in combination with radiotherapy. This study is recruiting patients with metastatic, castrate resistant prostate cancer.
Following DARRT-1, a series of studies will be undertaken with the objectives of showing the ability of NOX66:
(i) to sensitise tumours directly to irradiation (shrinkage/remission within tumours at sites of irradiation), and
ii) to stimulate an abscopal response in tumours not directly exposed to or affected by radiation.
Future studies will focus on patients with solid cancer types, who are suitable to receive radiotherapy to manage the symptoms and effects of the cancer (e.g. pain and discomfort). This treatment is known as “palliative radiotherapy”. The hypothesis of using NOX66 in combination with palliative radiotherapy is that the combination treatment will bring therapeutic benefit for the patient, with a tolerable side effect profile. The clinical development program will include large randomised trials in common cancers (e.g. prostate, lung) where use of NOX66 will be compared to treatment without NOX66 – this will allow direct comparisons in treatment. Smaller trials of patients with rare and less common cancers – a great unmet need – will be conducted in parallel to support the use of NOX66 across a wide range of cancers.
B. NOX66 plus targeted radiotherapy:
A major area of advancement in the treatment of patients with cancer is the use of targeted radiotherapies. The goal of these new therapies is to deliver radiation by injection directly in to tumour cells, leading to a greater therapeutic outcome, with less effect on healthy cells compared with standard chemotherapy and radiotherapy. Noxopharm believe that NOX66 may enhance the effects of these newer treatments in the same way that it may enhance the effect of radiotherapy delivered externally.
The first NOX66 study with targeted radiotherapy is underway. This study, known as LuPIN, involves patients with late-stage metastatic prostate cancer receiving experimental treatment with 177Lu-PSMA-617. PSMA can target prostate cancer cells throughout the body (i.e. metastatic tumours) with radioactive Lutetium providing an anti-cancer effect. This initial study will provide evidence of whether NOX66 may boost the effects of 177Lu-PSMA-617. A second study is in planning, to directly compare the effects of using NOX66 with patients receiving 177Lu-PSMA-617 alone. Noxopharm also plan to investigate the benefit of adding NOX66 to other tumour specific radiation therapies.
CHEMOTHERAPY - CEP program
The objective of the Chemotherapy Enhancement Program (CEP) is to enhance the cancer-killing abilities of standard cytotoxic chemotherapy drugs (such as carboplatin) through NOX66 providing both:
- a direct cytotoxic effect in its own right (additive effect), and
- blockage of the ability of the cancer cell to repair the damage caused by the chemotherapy drug (synergistic effect).
CEP1:This is a Phase 1a/Phase 1b sighting study in patients with late-stage, metastatic, solid cancers (of type ovarian, prostate, lung or breast). Patients received NOX66 at one of two doses (400mg or 800mg daily) in combination with carboplatin, initially at a dose lower than the standard single dose and then progressing to a higher dose of carboplatin. The study completed in May 2018, with results presented at the American Society for Clinical Oncology on June 4th. The results of the study have shown NOX66 in combination with carboplatin is well tolerated, with signals of response allowing for the development of further studies of NOX66 in combination with platinum-based chemotherapies such as carboplatin.