PDS Biotechnology and NCI Restart Phase 1/2 Trial of PDS01ADC and M7824 Combination for Kaposi Sarcoma
Combination of Next-Generation Immuno-Oncology Therapies
Led by the National Cancer Institute (NCI), this Phase 1/2 trial (NCT04303117) evaluates the combination of PDS01ADC (NHS-IL12/M9241), a tumor-targeted interleukin-12 (IL-12) immunocytokine, and M7824 (bintrafusp alfa), a dual-target immune checkpoint inhibitor. PDS01ADC binds to DNA in necrotic tumor tissue, delivering IL-12 to activate immune cells precisely within the tumor microenvironment, thereby significantly reducing systemic toxicity. When combined with M7824, a dual-target fusion protein that simultaneously inhibits PD-L1 and TGF-beta (TGF-Ξ²), the treatment strategy aims to remove immune-inhibitory barriers and maximize the efficiency of immune cell attack. This combination of precision-targeted delivery and dual immune checkpoint inhibition is expected to overcome the limitations of existing single-agent immunotherapies and generate synergistic effects.
Addressing Unmet Needs in the Rare Cancer Market
The primary target of this clinical trial, Kaposi Sarcoma, is a rare cancer primarily affecting immunocompromised patients and transplant recipients, with very limited treatment options. The global Kaposi Sarcoma treatment market is estimated to be approximately $105.041 million by 2026, with pegylated liposomal doxorubicin chemotherapy as the standard treatment. However, due to the strong systemic side effects and resistance issues of traditional chemotherapy, the introduction of new immunotherapy combinations with reduced toxicity and the ability to restore immune function is urgently needed. In particular, a strategy that simultaneously inhibits the immune-suppressive factor TGF-beta and directly stimulates immune responses via interleukin is gaining attention as an ideal alternative.
Merck KGaA and PDS Partnership Structure
PDS Biotechnology secured an exclusive global development and commercialization license for PDS01ADC in December 2022 through a licensing agreement with global pharmaceutical company Merck KGaA. The deal includes a non-refundable upfront payment of $5 million, $5 million in equity allocation, and potential milestone payments totaling $116 million based on future commercialization achievements. Meanwhile, M7824 is a drug developed in-house by Merck KGaA, which previously had a large-scale co-development agreement with GSK but faced setbacks due to clinical failures. This NCI-led trial now aims to explore new indications for M7824. The strategic positioning of leveraging collaboration with external government agencies to share development risks while maximizing the commercial value of proprietary assets is particularly notable.
Trial Design and Future Timeline
The trial aims to enroll a total of 80 patients, with primary endpoints including safety, maximum tolerated dose (MTD), and objective response rate (ORR). PDS01ADC will be administered every four weeks, and M7824 every two weeks, with treatment continuing for up to 96 weeks. Patient recruitment is progressing smoothly under the strict oversight of the National Cancer Institute (NCI), with a final completion date scheduled for December 1, 2028, allowing for long-term market value assessment. If the trial is successfully conducted, it could lead to expansion into other rare cancer indications and additional financial opportunities such as licensing agreements.
This Phase 1/2 trial is drawing industry attention as it explores the potential of an innovative immunotherapy combination to replace the current standard chemotherapy, which is primarily based on pegylated liposomal doxorubicin in the Kaposi Sarcoma market, valued at approximately $150 million annually. In the short term, the trial will provide safety and objective response rate (ORR) data for the combination of PDS01ADC and M7824, serving as an opportunity to validate the platform reliability of PDS Biotechnology (PDSB). In the medium to long term, it could secure a fast-track approval and commercialization pathway in the rare cancer field, where approved therapies are scarce, enabling the establishment of an exclusive market position. This trial is also expected to serve as a key milestone in re-evaluating the clinical potential of M7824, which previously had its co-development with GSK terminated, and in realizing the $126 million licensing agreement value between Merck KGaA and PDS.
Source: ClinicalTrials.gov (api_ct)