PharmaShots Interview: SOTIO’ Richard Sachse Shares Insight on SOT101 for the Treatment of Advanced/Metastatic Solid Tumors

In an interview with PharmaShots, Richard Sachse, Chief Medical Officer & Managing Director at SOTIO shared his views on the data of SOT101 in the P-I/Ib (AURELIO-03) study for the treatment of advanced/metastatic solid tumors

Shots:

The P-I/Ib (AURELIO-03) study evaluates SOT101 as monothx. & in combination with pembrolizumab in patients with advanced/metastatic solid tumors
The results showed that 13 patients with SOT101 + pembrolizumab had a clinical benefit, 3 with confirmed PR & 4 with SD, were well tolerated & encouraging efficacy signals in the 30 patients in the monothx. arm with 1 confirmed clinical & radiological response, 4 with SD
In the biomarkers analysis, SOT101 activates the innate & adaptive immunity, induced a robust immune-stimulatory response in multiple types of tumor microenvironments, dose-dependent PD response in the blood in both arms, increased CD8+ T cell & NK cell infiltration in clinically responsive patients

Tuba: Discuss the results of Phase 1/1b study of SOT101 in-depth during SITC

Richard Sachse: The combination of SOT101 with pembrolizumab in the AURELIO-03 study, showed that the majority of the initial 13 patients with advanced/metastatic solid tumors had the clinical benefit, including checkpoint inhibitor (CPI) refractory patients. In this dose-escalation study, investigators to date have observed three confirmed partial responses and four instances of long-lasting stable disease. These patients had a median of two lines of prior therapy (range 1-6). In addition, SOT101 in combination with pembrolizumab was generally well tolerated. Dose escalation in this study is ongoing until the definition of the recommended Phase 2 dose.

A SOT101 monotherapy arm of the study demonstrated encouraging efficacy signals in the 30 patients with advanced/metastatic solid tumors, including CPI refractory patients. To date, there has been one confirmed clinical and radiological response and confirmed the stable disease in four patients. Additionally, one patient responding on SOT101 monotherapy responded a second time to combination therapy with SOT101+pembrolizumab after experiencing a relapse on SOT101 monotherapy. SOT101 was well tolerated, and the majority of treatment-emergent adverse events were Grade 2 or less. Patients in this dose-escalation study have had a median of three lines of prior therapy (range 1-9). The recommended Phase 2 dose has been defined at 12 μg/kg and a Phase 2 monotherapy expansion study at this dose is ongoing in selected tumor indications.

An analysis of biomarkers in the study shows that SOT101 activates both innate and adaptive immunity. Key data shows that SOT101 induced a robust immune-stimulatory response in various types of tumor microenvironments. Investigators observed a dose-dependent robust pharmacodynamic response (CD8⁺ T cell and NK cell stimulation) in the blood of all patients in the monotherapy and SOT101+pembrolizumab arms, and clinically responsive patients showed increased CD8⁺ T cell and NK cell infiltration in the tumor. Furthermore, SOT101 restored the sensitivity to CPIs in CPI refractory/resistant patients.

Tuba: Can you please share the trial design of the Phase 1/1b study (which tumor patients are included in the solid tumor population)?

Richard Sachse: A multicenter open-label phase 1/1b study of SOT101 as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors.

Tuba: Tell us more about SOT101

Richard Sachse: SOT101 is a subcutaneously administered IL-15 superagonist that is fused to the sushi+ domain of the IL-15 receptor α chain. The drug has been precisely designed and optimized for its use as potent immunotherapy by addressing two important design issues that limit current IL-2 and IL-15 approaches:

Specificity for cytotoxic T and NK cells may provide superior efficacy and safety profile:
SOT101 is designed to selectively bind only to cytotoxic T and NK cells while avoiding other cell types that are associated with adverse events
Optimized half-life may improve efficacy by limiting T cell exhaustion:
SOT101’s pharmacokinetic properties enable it to ideally stimulate T and NK cells through pulses in cytokine concentration, rather than tonic stimulation

SOT101 has demonstrated strong preclinical in vivo efficacy in various tumor models showing increased long-term survival and tumor regression, as well as a favorable toxicology profile. SOT101 has been shown in pre-clinical models to synergize with checkpoint inhibitors and antibody therapies exerting ADCC.

Tuba: Why would you choose Merck’s pembrolizumab as a combinational partner for SOT101?

Richard Sachse: SOT101’s mechanism of action as a pure IL-15 receptor agonist, provides the promising potential for a combination approach with checkpoint inhibitors. SOT101 in combination with KEYTRUDA has shown promising clinical efficacy across multiple indications in our ongoing phase 1/1b AURELIO-03 study. We are excited to continue to collaborate with MSD, a global leader in oncology, to continue studying the combination as part of the AURELIO-04 study for the treatment of certain patients with solid tumors while exploring the full potential of SOT101. We look forward to advancing SOT101 to the benefit of patients globally.

Tuba: Out of these (above-mentioned) indications which indication does SOTIO plans to assess in the next levels?

Richard Sachse: SOTIO will conduct a Phase 2 open-label, multicenter study of SOT101 in combination with KEYTRUDA to evaluate efficacy and safety in patients with selected advanced or refractory solid tumors. The study is expected to treat up to 300 patients with a combination of SOT101 and a standard dose of KEYTRUDA. The study will enroll patients in the U.S. and selected European countries across six different indications, including certain types of non-small cell lung cancer, cutaneous squamous cell carcinoma, colorectal cancer, hepatocellular carcinoma, prostate cancer, and ovarian cancer.

Tuba: How does SOT101 differ from the other therapies available and pipeline?

Richard Sachse: SOT101 differs from other available therapies because it is a subcutaneously administered IL-15 superagonist that has been demonstrated in preclinical models to induce tumor regression resulting in increased long-term survival while exhibiting a favorable toxicology profile. It has also been shown in pre-clinical models to synergize with checkpoint inhibitors and antibody therapies exerting ADCC. Initial clinical data seem to confirm results from preclinical models.

Tuba: When can we expect the data of the P-ll study of SOT-101?

Richard Sachse: The Phase 2 AURELIO-04 study will be conducted in the U.S. and select European countries, beginning in the first half of 2022. Predefined interim analyses will provide initial and later robust data from the first half of 2023 over the next three years, which will further guide the development strategy.

Source: Verywell Health

About Author:

Richard Sachse is the Chief Medical Officer & Managing Director at SOTIO. He has more than 25 years of experience as a physician and scientist & has extensive expertise in pharmaceutical development covering the entire value chain from preclinical to registration. He holds a degree in medicine from the Friedrich-Alexander-University Erlangen, Germany, and board certification in Clinical Pharmacology.