LiPax Elicits Encouraging RFS Rate in Non–Muscle Invasive Bladder Cancer

Michael Oefelein, MD

LiPax (TSD-001), a precision-targeted, locally-delivered taxane, was found to induce a recurrence-free survival (RFS) rate of 83% in patients with non–muscle invasive bladder cancer (NMIBC) who had undergone transurethral resection of bladder tumor (TURBT), according to findings from the phase 1/2a TD-001 study (NCT03081858).¹

At 2 years of follow-up, the RFS rate was just 49% in patients who had received current standard-of-care (SOC) treatments.

At both 1 and 2 years, LiPax was found to be well tolerated, with no patients experiencing a change in urinary health-related quality of life. No dose-limiting toxicities (DLTs) were reported with the therapy, and investigators did not observe any evidence of systemic exposure to paclitaxel, which is the active ingredient of LiPax.

Notably, patients who received the therapy did not report toxicities like burning pain, discomfort, and urinary frequency—effects that are typically experienced with current SOC therapies for the disease.

“This 2-year follow-up data reaffirms the results of this study’s initial readout, which is that the target tissue penetration achieved by LiPax’s precision liposomal technology has the potential to improve patient outcomes without the tolerability concerns of current SOC therapies,” Michael Oefelein, MD, chief medical officer of LIPAC Oncology, stated in a press release. “We look forward to advancing LiPax into phase 2b trials this year, bringing us one step closer to providing patients in need with this innovative new treatment option.”

LiPax is a locally delivered formulation of paclitaxel, which is known to be very active in the systemic treatment of patients with urothelial carcinomas; the drug is lipophilic and not solubilized in the acidic environment of the bladder.² However, the chemotherapy agent is known to be associated with systemic toxicity that can result in adverse effects (AEs) like hearing peripheral neuropathy, hearing loss, and low blood count, among others.

Investigators are leveraging LiPax to strengthen permeation and solubility and to overcome barriers faced with paclitaxel regarding intravesical delivery. LIPAC Oncology, the drug developer, has conducted preclinical and clinical trials that have showed superior efficacy of intracavitary drug delivery, and the success is attributed to the following factors: lethality, persistence, and penetration.

Results from in vitro studies have found that the therapy is highly active against metastatic bladder cancer, with the therapy proving to be 200-fold more effective than mitomycin C. Other benefits of the formulation include stronger tolerability without significant systemic toxicity and optimized off-load-kinetics and intratumoral concentration that is comparable to paclitaxel.

LiPax is prepared as a dry powder, which diminishes the risks of scale up and manufacturing, and it can be stored in office and safely transported without degradation issues that are commonly experienced with liposomal formulations.

In the open-label, single-arm, multicenter phase 1/2a TD-001 trial, investigators set out to examine the safety and efficacy of LiPax via intravesical administration in patients with low- to intermediate-risk NMIBC, following TURBT.³

The trial design is prospective, non-randomized, and adaptive. In the trial, 2 cohorts, with 3 patients enrolled to each, were given 6 escalating intravesical doses of the agent (range, 10 mg to 540 mg) every 2 weeks. Treatment was given until DLTs were reported. AEs were defined per the NCI CTCAE version 5.0. Urinary symptom burden was looked at by using the IPSS and OAB-q instruments. Through the use of a validated assay, investigators bioanalytically measured paclitaxel urine and plasma concentration. Bladder tumor recurrence was evaluated through cystoscope and biopsy.

Earlier data from the trial showed that only 8 AEs were reported with LiPax, and all of them were grade 1 or 2; these effects included urinary tract infection (n = 2), worsening constipation (n = 1), bladder calculus (n = 1), post treatment–hematuria (n = 1), fatigue (n = 1), insomnia (n = 1), and hypersomnia (n = 1). Notably, none of these toxicities met the criteria for a DLT.

Additionally, no change in the IPSS or OAB-q scores was observed from baseline, and no measurable plasma concentrations of paclitaxel were observed across all doses evaluated (range, 10 mg to 150 mg). Urine paclitaxel concentrations showed a proportional increase in concentration as the dose increased. At a mean follow-up of 15 months, no evidence of clinical recurrence was observed among the 6 patients analyzed.

“There are currently limited treatment options for low-intermediate risk [patients with] NMIBC, and up to half of these patients will recur within 2 years,” said Neal Shore, MD, director of the Carolina Urologic Research Center and principal investigator of the agent. “Current post-TURBT drug treatment regimens have shortcomings for both patients and providers, including toxicities and supply shortages, which highlights the critical need for a treatment option that can improve patient outcomes without bothersome AEs.”

The FDA has given the green light to phase 2b and phase 3 trials examining Lipax. The phase 2b trial is anticipated to launch in Q4 2021.

LiPax is currently under preclinical development for upper tract urothelial carcinoma, ovarian cancer, intraperitoneal carcinoma, and mesothelioma/malignant pleural effusion.

References

1. LIPAC Oncology announces two-year recurrence free survival data for phase 1/2a study of LiPax in patients with non-muscle invasive bladder cancer. News release. LIPAC Oncology LLC. June 9, 2021. Accessed June 16, 2021. https://prn.to/3wxvzp2
2. LiPax: proliposomal intracavitary paclitaxel technology for targeted chemotherapy. LIPAC Oncology LLC. Accessed June 16, 2021. https://bit.ly/2U2p13c
3. LIPAC Oncology announces presentation of data from phase 1/2a study of LiPax in patients with highly recurrent bladder cancer. News release. May 18, 2020. Accessed June 16, 2021. https://prn.to/2SxVgHo