Clinical Overview

The primary objective of the clinical development program is to develop Veyonda® as an enhancer of radiotherapy, converting the effect of radiotherapy in advanced cancers from palliative to curative.

Two separate programs are underway:

  • DARRT program
  • LuPIN program.

Veyonda® and the DARRT program

DARRT stands for Direct and Abscopal Response to RadioTherapy.

A DIRECT response refers to the effect of radiotherapy on the tumours being exposed to radiation.
An ABSCOPAL response refers to the effect of radiotherapy on the tumours outside of the field of radiation.

The typical patient is one with late-stage cancer presenting for palliative radiotherapy. In this situation, 1 or 2 large tumours might be causing symptoms (pain or pressure on vital organs such as the spine) and the radiotherapy is being used to shrink those tumours to provide temporary symptomatic relief.

At the very least, we are anticipating that Veyonda® will lead to a better DIRECT response as a result of its ability to hold cancer cells in a state making them more vulnerable to damage by radiation, and then exacerbate that situation by blocking the cancer cell’s ability to repair the damage.

At most, we are anticipating that Veyonda® will lead to a better DIRECT response plus an ABSCOPAL response.

FAQs about Veyonda® and DARRT 

  1. What cancers are suitable for this approach?
    Veyonda® targets proteins that to date have been identified on all forms of cancer. We are focusing our initial clinical studies on prostate cancer, lung cancer and sarcomas, but we expect eventually to see the V-DARRT approach being used across the cancer spectrum.

  2. What does the V-DARRT program entail ?
    The entire treatment period is 3 weeks in 3 steps.

    Step 1: Veyonda® is given daily for 7 days prior to radiotherapy. This is to give time to load the tumours with drug to maximise the number of cancer cells being blocked in their G2M stage of cell division.

    Step 2: Radiotherapy (either external beam radiotherapy or stereotactic body radiotherapy) then is given over 5 days (using a radiation dosage of 4-5 Gy per day) to a single large tumour, along with Veyonda® each day.

    Step 3: Veyonda® is dosed daily for 7 days post-radiation to cover the ongoing effect of radiation.

  3. What side-effects can be expected?
    Veyonda® targets proteins generally not found in healthy cells and no adverse effects on healthy cells are known. No significant side-effects beyond mild to moderate levels of fatigue have been encountered in clinical studies to date with Veyonda® either on its own or in combination with radiotherapy. Nevertheless, further clinical studies will be needed to confirm this apparently good level of tolerability.

  4. How is Veyonda®given?
    Veyonda® is administered at home as a suppository twice daily.

Veyonda® and the LuPIN program

The LuPIN (Lu-PSMA IN Conjunction with Veyonda®) involves men with late-stage metastatic prostate cancer where instead of delivery radiotherapy externally, the radiation is injected intravenously in conjunction with Veyonda® treatment.

The radiation is in the form of the radionuclide, 177-lutetium, delivered attached to the peptide, PSMA-617. The peptide is the delivery vehicle and the 177-lutetium is the payload. The PSMA-617 seeks out the protein, PSMA, which is found mainly on prostate cancer cells, but also salivary gland, kidney and stomach cells. Once attached to the prostate cancer cells, the 177-lutetium delivers radiation that seeks to inflict maximal damage on the cancer cell and little or no damage on surrounding healthy tissue.

Lu-PSMA-617 therapy is an experimental therapy for late-stage, metastatic, castrate-resistant prostate cancer that is attracting considerable attention globally.

The Lu-PSMA-617 is injected intravenously on 6 occasions 6 weeks apart (= total 36 week treatment course). Current experience with this treatment is that roughly one-third of men fail to respond (based on PSA levels), another third show initial response but relapse before completing the 36-week course, and the final third complete the 36-week course with ongoing PSA response.

The rationale in using Veyonda® in conjunction with Lu-PSMA-617 is that Veyonda® will result in an improved DIRECT response to the radiation, with the objective of having more men remain on the 36-week treatment course.

FAQs about Veyonda® and LuPIN 

  1. How is this approach being tested?
    Veyonda® and Lu-PSMA-617 currently are being tested in a Phase 1b investigator-initiated study in Australia. It is a dose-finding study using both 400mg and 800 mg Veyonda® dosages.

  2. What does the program entail ?
    A treatment cycle is Veyonda® daily for 10 days starting 1 day prior to receiving an intravenous injection of Lu-PSMA-617. Each patient receives 6 treatment cycles.

  3. What end-points are being looked at?
    The two key end-points are safety and clinical response being monitored on the basis of PSA levels and clinical evaluations at 3, 6 and 12 months.