by Jakub Jarolím, Business Intelligence Department
by Jakub Jarolím, Business Intelligence Department
Stocks around the world fell and oil prices plunged, after evidence of a new coronavirus variant in South Africa prompted another round of travel restrictions and reignited concerns about the economic toll imposed by the pandemic.Nasdaq Biotech Index lost 4% during November.
A unique ADC, which delivers a high dose of a cancer-killing drug to tumor cells through a targeted antibody, has been found in a global phase 3 clinical study to nearly double the survival time of patients with refractory metastatic triple-negative breast cancer. The study of the ADC drug sacituzumabgovitecan (SG), reported superior outcomes compared to single-agent chemotherapy, the standard for treating metastatic triple-negative breast cancer. The phase 3 results of the study, known as ASCENT, were published in the New England Journal of Medicine. SG, which was developed and is manufactured by Immunomedics, a subsidiary of Gilead Sciences, received accelerated approval by the U.S. Food and Drug Administration in April 2020 on the basis of favorable phase 1/2 clinical trials, with full approval contingent on the confirmatory phase 3 results. ASCENT is a global study to evaluate the safety and efficacy of the antibody drug conjugate compared to chemotherapy in 529 patients with metastatic triple-negative breast cancer whose cancer had relapsed or was resistant to at least two other forms of therapy. The investigators found that median progression-free survival with the ADC agent was 5.6 months compared to 1.7 months with chemotherapy, and that median overall survival was 12.1 months with the ADC agent compared to 6.7 months with chemotherapy. The study also found that the response rate – that is, shrinkage in the size of the metastatic tumor sites – was 35% after administration of ADC compared to 5% with chemotherapy.
Interleukin-15 and Interleukin-2
SOTIO Biotech announced new data from the ongoing Phase 1/1b AURELIO-03 study of SOT101, an IL-15 superagonist, as a monotherapy and in combination with pembrolizumab in patients with advanced/metastatic solid tumors.In a combination of SOT101 with pembrolizumab in the AURELIO-03 study, the majority of the 13 patients with advanced/metastatic solid tumors had clinical benefit, including in 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. A SOT101 monotherapy arm of the study demonstrated encouraging efficacy signals in the 30 patients with advanced/metastatic solid tumors, including in CPI refractory patients. To date, there has been one confirmed clinical and radiological response and confirmed stable disease in four patients. Additionally, one patient had a partial response on SOT101+pembrolizumab combination therapy after experiencing a relapse on SOC101 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.
Affimed’s recent string of positive data for AFM13 continued with an impressive early efficacy report for the bispecific Innate Cell Engager in Hodgkin lymphoma patients, but investors still want to learn more about the treatment’s durability. Affimed reported that AFM13, a bispecific NK cell engager targeting CD30 on tumor cells and CD16A on NK cells, conjugated to allogeneic NK cells, led to a 100% ORR with five complete responses (42%) among the first 12 patients treated at the recommended Phase 2 dose in an open-label Phase 1/2 study. The trial enrolled patients with NHL and HL; 11 of the 12 patients in the highest dose cohort had Hodgkin lymphoma. Patients had progressed on a median of six prior lines of therapy. The data represent responses after the first of two planned cycles of treatment, which involved an infusion of the pre-complexed innate cell engager and NK cells, followed by weekly infusions of the innate cell engager alone for three weeks.
Other Innovative Treatment Areas
Oncorus offered initial safety, tolerability and immune activation and clinical response data from its ongoing Phase 1 trial with ONCR-177 at SITC. In the fully enrolled and completed surface-lesion, dose-escalation part of the study, single-agent ONCR-177, an oncolytic herpes simplex virus for intratumoral injection, proved well-tolerated with no dose-limiting toxicities. As of the Nov. 8, 2021, cutoff date, three of eight evaluable patients at the recommended phase II dose of 4x108 PFU in 4 mL with cutaneous melanoma, squamous cell carcinoma of the head and neck, and mucosal melanoma, showed clinical benefit after two doses of the compound, which will also be tried in combination with Merck’s anti-PD-1 Keytruda.
SOTIO Biotech announced an exclusive, target-specific license and option agreement with LegoChem Biosciences. SOTIO will obtain rights to deploy LegoChem’s ADC technology for up to five therapeutic programs targeting distinct tumor-associated antigens.The deal enables SOTIO to combine its proprietary antibodies with LegoChem’s ADC technology platform in order to deliver novel therapeutics for the treatment of solid tumors and includes LegoChem’s proprietary conjugation technology ConjuAll and potent linker-payload platform including multiple different payloads.LegoChem is eligible to receive upfront and potential milestone payments worth up to $1027.5 million, payable based on certain developments and regulatory achievements, plus royalties on net sales. The deal includes upfront and near-term milestones worth up to $29.5 million, subject to exercise of the options and achievement of success-based milestones.SOTIO will be responsiblefor R&D,manufacturing,andcommercializationof the ADC products, while LCB will support and work closely with SOTIO for the research activities and the manufacturing of components that are specifically related to its proprietary ConjuAll and the linker-payload technologies.