Highlight Therapeutics has revealed what it called “potentially game-changing” early results from the Phase 2b clinical trials of its lead drug in combination with a leading immunotherapy drug.
Chief executive Dr Marisol Quintero said the privately-owned company is now in the planning stage of a pivotal Phase 3 trial, due to begin in 2022, and is starting to talk to potential partners about other combinations.
The Phase 2 study is testing Highlight’s BO-112 drug in combination with a leading anti-PD1 immunotherapy as a second-line treatment on 37 melanoma patients who have shown anti-PD1 resistance. In other words, the drug combination is being given to patients who have previously had no success with immunotherapy treatments for their skin cancer.
Highlight said the trial has met its primary endpoint with a 65% disease control rate, where the melanoma is prevented from growing, plus a 27% preliminary overall response rate (ORR) that includes 8% complete responses, where the tumour has reduced in size.
Dr Quintero said: “This initial data is very encouraging and has the potential to change medical practice.”
She said the preliminary ORR and complete responses already exceed current standards of care, such as the use of anti-CTLA-4 immunotherapy.
Some sub-groups of patients also showed notable results, including hard-to-treat mucosal melanoma patients achieving 66% ORR and 100% disease control rate.
Based on the drug’s mode of action and experience from Phase 1 studies, Quintero and the team expect follow-up data from these patients will show further improvements in the ORR by the time full results are published in the spring.
Executive chairman Dr Carlos Paya called the result “potentially game-changing” as they show BO-112 “can rescue melanoma patients who have failed first-line immune-therapy with anti-PD1”.
He added: “Anti-PD1 based immunotherapy has revolutionized oncology treatments, but only a fraction of patients initially respond and many of these patients progress thereafter. These initial Phase 2 results show that BO-112 combined with a leading PD1 inhibitor rescue around 65% of anti-PD1 failing patients, making many of them respond to the combined treatment.
“These much-anticipated outcomes demonstrate BO-112’s potential as a best-in-class therapy for melanoma patients whose disease has progressed on prior anti-PD1 treatment, and we now look forward to further clinical studies, not only in melanoma but in other major tumor types in which anti-PD1 resistance is also an issue.”
The market for anti-PD1 therapies is valued at roughly US$24bn, according to the IQVIA Global Oncology Report, with the drugs used across most solid tumours – although currently fewer than 20% of all cancer patients benefit from first-line anti-PD1 treatment.
BO-112 in combination with an anti-PD1 therapy is designed to ‘resensitize’ tumors to anti-PD1 treatment by a dual action of making the tumour cells more visible to the immune system as well as ‘training’ the body’s T-cells to target the cancer cells.
In this Phase 2 trial, BO-112 is being given in combination with Merck & Co’s (MSD) Keytruda anti-PD1 immunotherapy.
The safety profile of combination has been exemplary, with no patients discontinuing the study due to adverse events.