Perspective Therapeutics, Merck Partner to Test [212Pb]PSV359 Plus Keytruda in FAP-α-Positive Solid Tumors
核心洞察
Perspective Therapeutics and Merck (搜索) signed a clinical trial collaboration and supply agreement to evaluate [212Pb]PSV359 (搜索) with Keytruda (pembrolizumab) in FAP-α-positive solid tumors.
The combination will be studied under an amendment to Perspective's ongoing Phase 1/2a trial (NCT06710756) in non-small cell lung cancer (搜索) and colorectal cancer (搜索), with the first three monotherapy dose cohorts fully enrolled.
Perspective is sponsoring the study and Merck (搜索) is supplying pembrolizumab at no cost, with the collaboration aiming to reshape the immunosuppressive tumor microenvironment.
Perspective Therapeutics, Inc. (NYSE AMERICAN: CATX) announced a clinical trial collaboration and supply agreement with Merck (搜索) (NYSE: MRK), known as MSD outside the United States and Canada, to evaluate the company's targeted alpha-particle therapy [212Pb]PSV359 (搜索) in combination with Keytruda (pembrolizumab), Merck's anti-PD-1 (搜索) therapy.
The combination will be assessed under an amendment to Perspective's ongoing Phase 1/2a study of [212Pb]PSV359 (搜索) in patients with certain types of non-small cell lung cancer (搜索) and colorectal cancer (搜索) that express fibroblast activation protein alpha (搜索) (FAP-α), according to the Sept. 14, 2026 announcement. The trial is registered under clinicaltrials.gov identifier NCT06710756 and has completed enrollment in its first three monotherapy dose cohorts.
Under the agreement, Perspective is sponsoring the study, while Merck (搜索) is providing pembrolizumab at no cost.
Rationale for Combining Radiotherapy and Checkpoint Blockade
The collaboration is built on the hypothesis that targeted radiation delivered to FAP-α-expressing tumor stroma may alter an environment that has historically resisted immunotherapy.
"FAP-α is associated with the majority of solid tumors and with a tumor microenvironment historically characterized by poor drug penetration and immune suppression or exclusion," said Markus Puhlmann, Perspective's Chief Medical Officer. "By combining targeted radiopharmaceutical treatment with a well-established immune checkpoint inhibitor, we aim to evaluate whether this approach can reshape the tumor environment and potentially improve treatment outcomes for patients with advanced FAP-α-positive solid tumors."
FAP-α as a Therapeutic Target
FAP-α is a protein abundantly expressed on the surface of cancer-associated fibroblasts (CAFs) in the stroma, a component of the tumor microenvironment in the majority of epithelial cancers. Beyond CAFs, FAP-α is also expressed on certain cancer cells themselves, including sarcomas and mesotheliomas.
Higher FAP-α expression has been associated with poor prognosis in a number of solid tumors, including non-small cell lung cancer (搜索), colorectal cancer (搜索), pancreatic cancer (搜索), stomach cancer, mesothelioma (搜索), head and neck cancer, esophageal cancer, and ovarian cancer. Expression of FAP-α in healthy tissues is usually low, a characteristic that supports its use as a tumor-selective target.
PSV359 Design and Theranostic Strategy
PSV359 was designed to target and deliver 212Pb to tumor sites expressing FAP-α, which is associated with multiple highly prevalent solid tumors in patients in need of additional treatment options. The targeting moiety may also be radiolabeled with 203Pb or 68Ga, known as PSV377, to detect FAP-α expression in individual patients.
Preclinical imaging and therapy as well as human imaging results suggest Perspective's proprietary targeting ligand has improved levels of target engagement and uptake in tumors, as well as reduced retention in healthy tissues, which may result in a desirable therapeutic index, according to the company.
Trial Design and Endpoints
Perspective is conducting a multi-center, open-label, dose-finding and dose-expansion study of [212Pb]PSV359 (搜索) in patients with advanced solid tumors that express FAP-α, as determined by imaging with [203Pb]PSV359. The primary objective of the dose-finding phase is to assess the safety and tolerability of various doses of [212Pb]PSV359 in order to determine the recommended Phase 2 dose for the expansion phase, where anti-tumor activity may be an additional primary outcome measure.
Broader Pipeline and Manufacturing Platform
Perspective Therapeutics describes itself as a radiopharmaceutical development company pioneering advanced treatments for cancers throughout the body. Its proprietary technology uses the alpha-generating isotope 212Pb to deliver radiation specifically to cancer cells via specialized targeting moieties, complemented by imaging techniques that incorporate the same targeting moieties — a "theranostic" approach intended to enable visualization of the specific tumor and subsequent treatment, potentially improving efficacy and minimizing toxicity.
The company is advancing a portfolio of clinical-stage programs in the U.S., including bamzireotide navoxetan (搜索) (VMT-α-NET, neuroendocrine tumors (搜索)), lapemelanotide zapixetar (搜索) (VMT01, melanoma (搜索)), and PSV359 (solid tumors). Perspective is also expanding its regional finished drug product candidate supply network, enabled by its proprietary 224Ra/212Pb generator platform used to manufacture clinical drug product candidates, to support delivery of patient-ready drug product candidates for clinical trials and, if approved, commercial operations.
Keytruda is a registered trademark of Merck (搜索) Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.