Convert Pharmaceuticals' Experimental Cancer Drug Shrinks Tumours in Patients Who Had Run Out of Options

Convert Pharmaceuticals today reported the first clinical results for CP-506, a cancer medicine designed to remain inactive in the body until it reaches the resistant low-oxygen regions of a tumour, where it is activated. 

In an ongoing early Phase 1 trial, patients who had exhausted available treatments showed clinical benefits and reductions in tumour volume after three treatment cycles. Tumour volume reductions ranging from 11% to 49% were observed in patients with breast, pancreatic, and head and neck cancers, despite extensive prior treatment. These patients received dose levels 3 or 4 in a dose escalation study designed primarily to establish safety. No dose-limiting toxicity has been observed. 

Reversing the paradigm of cancer treatment 

Conventional chemotherapy circulates throughout the body, while typically less than 1% of the administered drug reaches the tumour. This broad exposure damages healthy tissues and causes systemic side effects. 

CP-506, the company's lead prodrug, reverses the arithmetic. It circulates harmlessly and converts into a potent anti-cancer agent only within the tumour, more specifically in the very low-oxygen regions inside tumours, conditions found nowhere else in the body. In short, the tumour manufactures the drug that destroys it (watch the animation). 

Oxygen-starved regions, known as hypoxic regions, occur in at least 50% of solid tumours and make cancers less responsive to immunotherapy, chemotherapy, targeted therapies, endocrine therapy and radiotherapy. Earlier efforts to target hypoxic tumours were hampered by limited patient selection and toxicity from drug activation outside the tumour. Those setbacks did not invalidate the underlying therapeutic idea. Our approach is designed to address both challenges: identifying patients whose tumours are hypoxic and using a drug engineered to avoid activation in well-oxygenated tissues. 

 “For decades, cancer treatment has faced a difficult trade-off: exposing the whole body to a drug while trying to kill cancer cells deep inside a tumour,” said Prof. Dr. Philippe Lambin, Founder and Chief Executive Officer of Convert Pharmaceuticals. “CP-506 is designed to change that equation. Our published research shows how the low-oxygen conditions found within tumours can activate the drug, while oxygen limits that activation elsewhere. Now, in our early clinical study, we are seeing tumour shrinkage in some patients whose cancers progressed despite previous treatments, even at doses below those we initially expected to show activity. These are early findings, but they give us a compelling reason to continue the investigation.” 

What the trial has shown 

CP-506 is a hypoxia-activated prodrug. Results come from the dose-escalation portion of the Phase I/IIa TUMAGNOSTIC trial (NCT04954599), at dose levels 3 and 4 out of 6. 

• No dose-limiting toxicity across four dose levels. No cohort expanded for safety concerns. 
• Tumour-restricted activation confirmed in humans with active metabolite present in plasma at roughly 1/70th of parent prodrug concentration; second metabolite undetectable in the circulation. 
• Elimination half-life of 5.6 hours, an order of magnitude longer than earlier hypoxia-activated prodrugs, the sustained exposure needed to efficiently reach poorly perfused tissue. 
• Stable disease by RECIST v1.1, with exploratory volumetric reductions in lesions of 49% and 25% (pancreatic, dose level 4), 37% (head and neck) and 11% (breast, both dose level 3). 
   

 “Hypoxia has resisted every attempt to drug it for decades. Convert appears to have solved that,” said Dr. Antonin de Fougerolles, founding Chief Scientific Officer of Moderna and former CSO of Ablynx Therapeutics. “Tumours shrinking in monotherapy at the lower doses of an escalation, with no meaningful toxicity, is well ahead of what anyone would expect at this stage and points to an unusually wide therapeutic window. I have long followed the company’s work and have backed their efforts to develop a new transformational approach to treating solid tumours and look forward to seeing what full doses and combinations deliver.”  

What happens next 

Escalation continues, and the remaining dose levels should roughly double exposure. CP-506 was designed as a combination agent, attacking the slow-growing hypoxic tumour core while standard therapies hit the fast-dividing oxygenated rim. The protocol includes arms combining CP-506 with carboplatin and with immune checkpoint inhibitors in a later, already approved Phase IIa. Imaging and blood biomarkers are being analysed to identify responders in advance.