The FDA has granted Fast Track designation to PT217, a bispecific antibody developed by Phanes Therapeutics, for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) who have progressed following platinum-based chemotherapy with or without a checkpoint inhibitor. This designation aims to accelerate the development and review of PT217, addressing a significant unmet need in this aggressive cancer.
Mechanism of Action
PT217 is a first-in-class native IgG-like bispecific antibody targeting DLL3 and CD47. Its unique mechanism is designed to kill tumor cells through antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cell cytotoxicity by NK cells. By dually targeting DLL3 and CD47, both expressed on the surface of cancer cells, PT217 aims to heighten antitumor activity. Additionally, it is thought to elicit tumor neoantigens by channeling tumor cells into phagocytotic antigen-presenting cells and stimulate the adaptive immune system by indirectly activating T-cell–mediated death of DLL3-expressing tumor cells through recognition of tumor neoantigens.
Clinical Development
PT217 is currently under evaluation in the Phase 1 SKYBRIDGE trial (NCT05652686), an open-label, dose-escalation and dose-expansion study. The trial is designed to evaluate PT217 in patients with advanced refractory cancers expressing DLL3, including SCLC, large cell neuroendocrine carcinoma (LC-NEC), neuroendocrine prostate cancer, or gastroenteropancreatic NEC with disease progression and no standard of care or tolerable treatment options available.
The primary objectives of the SKYBRIDGE study include determining any dose-limiting toxicity, the maximum tolerated dose, the recommended phase 2 dose (RP2D), and the overall safety of PT217. Secondary objectives include measures of efficacy, quantified by objective response rate and pharmacokinetics, as well as the disease control rate.
The Need for New SCLC Therapies
Small cell lung cancer is an aggressive form of cancer characterized by high mortality rates and significant morbidities. The average survival for patients who present with ES-SCLC without treatment is 2-4 months after diagnosis; the median survival for patients with treatment is 7-11 months. The current standard of care includes platinum-based chemotherapy, often in combination with checkpoint inhibitors; however, many patients experience disease progression, highlighting the urgent need for novel therapeutic options.
Executive Perspective
"PT217 has the potential to be a transformative treatment option for patients with SCLC, LCNEC and EP-NECs in various settings," said Ming Wang, Founder and CEO of Phanes Therapeutics. He also noted the significance of having two Fast Track designations in their pipeline, with PT886 also receiving the designation for metastatic claudin 18.2-positive pancreatic adenocarcinoma. Wang believes their optimized anti-CD47 bispecific antibody approach can unlock the full potential of the innate immunity in targeting solid tumors.
