The IMP-MEL clinical trial has begun with its first patient being dosed with the new drug PORT-2 today in Oxford. The Oxford-led study is investigating the tolerability and efficacy of PORT-2, a drug that was developed to target iKT and trigger a cancer-specific B and T-cell response to tumours.
The IMP-MEL study is expected to enroll 100 patients in Oxford and other centres, and will evaluate PORT-2 both as a monotherapy and in combination with approved PD-1 inhibitor drug Keytruda in the treatment of Melanoma and Non-Small Cell Lung Cancer (NSCLC).
An additional exciting aspect of the PORT-2 drug is that it has the potential to re-sensitize checkpoint-resistant tumours to treatment with PD-1 antibodies. Not all patients’ tumours respond to current immune-oncology agents, with most cancer types are totally insensitive to treatment. Re-sensitising patients is one approach to make existing cancer drugs more effective and appropriate in the treatment of multiple patient’s cancers.
Mark Middleton, Departmental Head of Oncology and Professor of Experimental Medicine at the University of Oxford, says;
“Checkpoint inhibitor therapies have enormous opportunity in the treatment of solid tumors, but unfortunately, many cancers develop a resistance to these therapies, leaving many patients without adequate treatment options,”
“We’re constantly seeking new therapies that are capable of addressing resistance and enabling a durable response in patients with cancer. Should PORT-2 prove successful, this novel iNKT agonist therapy could potentially re-sensitize patients to checkpoint inhibitor treatment and could activate that durable immune response. It’s a very exciting new avenue for oncology research.”
This trial is being led by Mark Middleton in Oxford with supply and funding from Portage Biotech Inc. The IMP-MEL study is supported by the NIHR Biomedical Research Centre.
Dr. Ian Walters, chief executive officer of Portage Biotech says;
“Preclinical data show that our iNKT agonist can stimulate a broad response from both the innate and adaptive immune systems, helping the body recognize and attack these cancers,”
“This first-in-human trial features a robust design with a multi-arm comparison against standard of care therapies currently used in the clinic, which we believe has the potential to accelerate our research as we evaluate the effectiveness of PORT-2 both as a monotherapy and in combination with PD-1 checkpoint inhibitors.”
About iNKT agonists PORT-2 and PORT-3
PORT-2 and PORT-3 contain small molecule agonists (IMM60) of invariant natural killer T-cells (iNKT cells) developed by the University of Oxford, which play an important role in anti-tumor immune responses. iNKT cells are a distinct class of T lymphocytes and recognize lipid antigens on the surface of the tumor. The synthetic iNKT agonists are designed to optimally engage the T-cell receptor on the iNKT and facilitate its binding to dendritic cells, resulting in the secretion of a large amount of pro-inflammatory cytokines. This leads to the activation and expansion of important immune system components and primes and boosts an adaptive immune attack against cancer.
Monotherapy treatment with iNKT agonists shows a heightened immune response and better cancer control in animal models that are resistant to PD-1 antibody treatment. Combination therapy with PD-1 antibodies is synergistic with iNKT agonists and restores sensitivity to PD-1 blockade. While treatment with iNKT agonists alone shows promising preclinical activity against cancer, data suggests that when an iNKT agonist is co-packaged with tumor-specific antigens, potency is increased by up to 5x. PORT-2 is a liposomal formulation of the IMM60 iNKT agonist while PORT-3 is a co-formulation of the IMM60 iNKT agonist with an NY-ESO-1 peptide vaccine, co-packaged into a nanoparticle.