Since Noxopharm’s ASX release last Wednesday about seeing abscopal responses in two patients receiving NOX66, some shareholders have asked me what it means to the future treatment of cancer. The short answer is, potentially a great deal. By any definition, it is ‘disruptive technology’ that has the potential to change the face of cancer therapy.
It offers the prospect of using a minimally invasive, well tolerated, relatively inexpensive treatment to produce a complete and durable remission of many forms of metastatic cancer.
The strict definition of an abscopal response means applying radiation in a relatively confined way to tumours in selected areas of the body and seeing a response in distant tumours well outside of the irradiated areas. Radiation works by damaging the cancer cells it passes through, hopefully creating enough damage to kill the cancer cells. So, applying radiation to a tumour on a patient’s arm and causing it to shrink, but then seeing another tumour (of the same type) on the patient’s leg also shrink, does seem counter-intuitive given our current understanding of how radiotherapy works.
After about 40 years of radiotherapy up until the turn of this century and the millions of cancer patients who would have undergone radiotherapy over that time, there were only 8 known reported cases of abscopal responses. So, it certainly wasn’t a very common occurrence, suggesting that radiotherapy on its own is highly unlikely to cause an abscopal response. There were lots of theories about what was going on in the few patients where it had occurred, but that is all they were….. theories.
That changed with the introduction of the so-called immuno-oncology cancer drugs about 14 years ago. These are drugs that seek to overcome the blockage that prevents the body’s immune cells from attacking cancer cells. Suddenly reports were surfacing of abscopal responses in patients being treated with a combination of immuno-oncology drugs and radiotherapy. Consequently, it has been hard to avoid the suspicion that the immune system is somehow involved in the abscopal response. The suspicion is that the body’s immune cells such as the natural killer (NK) cells have managed to become activated against the damaged/dying cancer cells, enabling them to attack intact tumours that haven’t been damaged by radiation.
A lot of clinical studies are now underway using a combination of immuno-oncology drugs and radiotherapy to see to what extent an abscopal response can be induced. It will be a while before we have that data. In the meantime, what we do have is a small number of reports where clinical data involving a combination of immuno-oncology drugs and radiotherapy has been mined for evidence of an abscopal response. Collectively, these reviews involve slightly fewer than 100 cases from which we can draw the following general conclusions:
- In certain cancer types such as melanoma and lung, the incidence of an abscopal response can be relatively high (30-40%).
- Most responses have been partial (either all non-irradiated tumours shrinking but not disappearing, or not all tumours shrinking); complete (100%) responses are uncommon.
- A patient is more likely to have an abscopal response when the tumours exposed to the radiotherapy respond.
- Patients who have an abscopal response, even a partial one, live significantly longer than those who don’t respond
- But, in almost every one of these cases, the tumour eventually relapses and the patient dies.
Noxopharm is pursuing the abscopal response phenomenon through its DARRT (Direct and Abscopal Response to RadioTherapy) clinical program. This involves taking patients with metastatic disease (multiple secondary tumours), treating them with NOX66 daily for 14-21 days, and exposing between 1 and 2 individual tumours to a palliative (low) dosage of radiation. 6 and 12 weeks later, we look to see what has happened to both the irradiated tumours and the non-irradiated tumours.
This approach differs from that being taken by the immuno-oncology drug studies in a number of important ways:
- NOX66 has multiple ways of contributing to an abscopal response. First, it appears to enhance the killing effect of radiation. This means that the tumours receiving the radiation are more likely to die in the presence of NOX66 and the current evidence suggests that that leads to a better abscopal response outcome. Second, it appears that NOX66 directly activates natural killer cells, the cells responsible for attacking cancer cells.
- Immuno-oncology drug treatment requires treatment over several months, is commonly associated with side-effects, and is expensive. NOX66 is delivered over 2-3 weeks and has proven to be well tolerated.
- Noxopharm is focusing on cancers currently showing poor response rates to immuno-oncology drugs. These include prostate, breast and ovarian cancers.
DARRT-1 in prostate cancer patients is underway, and we expect to be able to provide an initial report on the 6-week scans of first 12 patients by July this year. DARRT-2 involving other cancer types will get underway once we have the 6-week data from the first 12 DARRT-1 patients.
One interesting outcome of DARRT-1, or any of the immuno-oncology/radiotherapy studies, if they are successful and if there is a strong and durable complete abscopal response in a high proportion of patients, is what effect it will have on the future of chemotherapy drugs currently under development.