Imugene reports positive early signals from Phase 1 trial of CF33-hNIS cancer killer

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By Imelda Cotton - 
Imugene ASX IMU Phase 1 CF33-hNIS virus VAXINIA intravenously intratumourally

A Phase 1 metastatic advanced solid tumours (MAST) trial evaluating the safety and efficacy of novel cancer-killing virus CF33-hNIS (VAXINIA) has delivered positive early signals for immuno-oncology company Imugene (ASX: IMU).

The study structure comprises 34 patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment.

Back in May 2022, the patients were dosed with CF33-hNIS alone or in combination with checkpoint inhibitor drug pembrolizumab (Keytruda), either intravenously (IV) or intra-tumourally (IT).

By the end of last month, the entire cohort had received VAXINIA during a continuing dose escalation phase where 16 patients had IT-administered doses and 18 had doses intravenously as monotherapy or in combination with pembrolizumab.

Of these, 25 patients were able to receive their first evaluation scan at day 42, with results showing that 16 had achieved stable disease (SD) status while eight registered progressive disease (PD) as measured by standard approaches including iRECIST ([immune] response evaluation criteria in solid tumours) and RECIST (response evaluation criteria in solid tumours).

Hard-to-treat cancers

Importantly, early results from six patients with hard-to-treat gastrointestinal cancers (including colorectal, bile duct, pancreatic and liver) who received CF33-hNIS alone showed positive treatment effects, with a disease control rate of 75%.

One patient registered a complete response (CR) at a mid-dose level over 350 days, and one had a partial response (PR) in melanoma at the same dose.

One patient with bile duct cancer who received IT-administered mid-dose levels of CF33-hNIS displayed pseudo-progression with a 49% increase in tumour burden after two cycles of therapy.

By the fourth cycle, that patient had achieved a complete response (iCR) with no known recurrence in the ensuing 200 days.

A second patient who had previously progressed on prior drug therapies, achieved SD status for approximately four months following IV-administered doses of CF33-hNIS.

Proceeding to plan

Imugene chief executive officer Leslie Chong said the trial had been proceeding to plan.

“Phase 1 trials are generally designed to look for safety, tolerability and early response signals to determine the optimal dose for further development… the early positive response data we are seeing at the mid-dose level in bile duct cancer suggests that VAXINIA may be a potent anti-cancer drug as we interrogate higher dose levels,” she said.

“The absence of any adverse safety signals allows us to dose higher so VAXINIA will have a very high therapeutic window which is valuable in oncology drug development.”

Difficult to treat

Bile duct cancers are difficult to treat and typically respond poorly to immunotherapy drugs.

Pseudo-progression is a phenomenon in which the cancer initially appears to grow (largely due to the cancer cells being infected by the virus) but is followed by infiltration of cancer-fighting immune cells.

This is typically followed by a decrease in tumour burden when the therapy takes effect.

Pseudo-progression can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to false impressions that the cancer is growing.

Trial recruits

Imugene’s Phase 1 MAST trial aims to recruit cancer patients across approximately 10 trial sites in the US and Australia, and is expected to run until May 2024.

A trial expansion has been planned for 10 patients with bile duct cancers.