Helix BioPharma Corp. has published peer-reviewed results from a Phase I/II clinical study demonstrating that its lead candidate L-DOS47 achieved statistically significant progression-free survival extension in heavily pretreated advanced non-small cell lung cancer (NSCLC) patients. The findings, published in Frontiers in Oncology, support advancing the first-in-class antibody-enzyme conjugate into combination therapy trials.
Novel Mechanism Targets Tumor Microenvironment
L-DOS47 represents a unique approach to cancer treatment as an antibody-enzyme conjugate (AEC) designed to selectively target CEACAM6-expressing solid tumors while locally neutralizing the acidic tumor microenvironment (TME). This dual mechanism addresses what researchers increasingly recognize as a critical barrier to efficacious cancer therapy.
The Phase I/II open-label study, initiated in 2012 across clinical sites in Poland and academic institutions in Canada, evaluated L-DOS47 as monotherapy in patients with advanced NSCLC. The study demonstrated that L-DOS47 was well tolerated at doses up to 13.55 μg/kg, establishing a favorable safety profile for the novel therapeutic approach.
Significant Survival Benefit in High-Dose Patients
While the study observed no complete or partial responses, post-hoc exploratory analyses revealed compelling efficacy signals. Patients receiving higher doses experienced a statistically significant extension in progression-free survival (PFS), with median PFS reaching 4.1 months (approximately 16 weeks) in the highest dosing quartile (P=0.0203).
This finding carries particular clinical significance given that over 90% of these patients had received two or more prior lines of therapy. For context, median PFS with pembrolizumab monotherapy in previously treated NSCLC populations typically ranges from 2 to 6.3 months, depending on PD-L1 expression levels.
CEACAM6 Emerges as Promising Biomarker
Immunohistochemical tumor tissue analysis of an unrelated cohort revealed that CEACAM6 was highly expressed in nearly half of NSCLC cases, supporting the exploration of biomarker-driven patient selection for future trials. This discovery positions CEACAM6 as a potentially valuable biomarker for identifying patients most likely to benefit from L-DOS47 treatment.
"This study supports the safety profile of L-DOS47 and highlights the importance of CEACAM6 as a new biomarker for biologics for the treatment of lung cancer," said Brenda Lee, corresponding author and Clinical Director at Helix. "It lays the groundwork for further development of L-DOS47 as part of combination strategies in CEACAM6-expressing cancers."
FDA Endorses Combination Strategy
Building on these monotherapy results, Helix BioPharma is advancing L-DOS47 into combination therapy trials. The company has received positive feedback from the FDA on its planned Phase I/II study combining L-DOS47 with the PD-1 inhibitor pembrolizumab.
"We're excited to build on these findings by advancing L-DOS47 into a new clinical study in combination with the PD-1 inhibitor pembrolizumab," said Thomas Mehrling, MD, PhD, CEO of Helix BioPharma. "By neutralizing tumor acidity, L-DOS47 has the potential to create a more favorable tumor microenvironment for immunotherapies like checkpoint inhibitors to work more effectively."
Expanding Pipeline Beyond NSCLC
Helix BioPharma's development strategy extends beyond L-DOS47, with the CEACAM6-targeting foundation supporting next-generation bi-specific antibody-drug conjugates currently in discovery. The company also advances two pre-IND candidates: LEUMUNA™, an oral immune checkpoint modulator for post-transplant leukemia relapse, and GEMCEDA™, a first-in-class oral gemcitabine prodrug designed to expand treatment options for advanced cancers.
The published results establish L-DOS47's safety profile while demonstrating meaningful clinical activity in a challenging patient population, setting the stage for combination approaches that could enhance the effectiveness of current immunotherapies in NSCLC treatment.
