[Edaily Reporter Yoo Jin-hee] #PenitriumBioScience, which has drawn attention from the global pharmaceutical and biotech industries by elucidating the mechanism of cancer metastasis—a problem that had remained unsolved in oncology for 137 years—has taken its first step toward a next-generation combination cancer drug clinical trial.

Penitrium Bio announced on the 17th that it is commencing a Phase 1 clinical trial combining its tumor microenvironment (TME)-targeted new drug candidate “Penitrium” with the global blockbuster immuno-oncology drug “pembrolizumab” (brand name: Keytruda).

Following the recent approval by the Ministry of Food and Drug Safety (MFDS) to change the formulation to tablets, administration will begin for patients with non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC) who have failed previous treatments, primarily at Ajou University Hospital and other institutions.

This Phase 1 clinical trial serves as a platform to validate in humans the “Seed & Soil” hypothesis of cancer metastasis, first proposed by Stephen Paget in 1889. Penitrium Bio’s research team has already demonstrated—for the first time worldwide—through experiments with patient-derived organoids that the new drug Penitrium preemptively blocks the three key factors that cause cancer metastasis.

Penitrium fundamentally disrupts the cancer ecosystem by controlling the microenvironment. Specifically, it employs three key anti-cancer mechanisms: △ disrupting the extracellular matrix (ECM)—where cancer cells take root—by suppressing the expression of collagen and fibronectin; △ inducing anoikis (cell death) in cancer cells that have lost their ability to adhere by inhibiting integrins; and △ inducing metabolic starvation by blocking oxidative phosphorylation.

This “soil-targeting” mechanism is regarded as a key game-changer that will break through the limitations of the global immuno-oncology market, valued at tens of trillions of won. Currently, patient response rates to immuno-oncology drugs remain at 20–30% due to the phenomenon of “pseudo-resistance,” in which tissues surrounding the tumor form a physical defense barrier. When Keytruda, which targets cancer cells (Seed), is co-administered with Penitrium, which renders the metastatic environment (Soil) inhospitable, this defensive barrier is completely dismantled, allowing dormant immune cells to penetrate the tumor and reactivate the drug’s efficacy.

This clinical trial is significant as a treatment strategy applicable across cancer types, as it confirms the potential efficacy of Penitrium in two distinct cancer types—breast cancer and lung cancer. Penitrium Bio plans to build on the initial data obtained from this immunotherapy combination trial—as well as the results of the ongoing clinical trial at Seoul National University Hospital for #Hyundai BioScience’s combination clinical trial for its prostate cancer hormone therapy (enzalutamide), as well as from this immunotherapy combination trial, and plans to use this as a springboard to pursue entry into a global Phase 2 clinical trial covering multiple targeted anticancer drugs—regardless of the specific targeted agent or cancer type—with the U.S. Food and Drug Administration (FDA).

Jin Geun-woo, CEO of Penitrium Bio, stated, “The three major metastasis-blocking mechanisms validated using patient-derived models represent a scientific innovation—a ‘first-in-class’ breakthrough that solves a long-standing challenge in oncology.” He added, “We will clinically demonstrate the dismantling of pseudo-resistance, which has been overlooked in modern cancer treatment, and establish a new global standard for combination cancer therapy.”

Cho Won-dong, Chairman of Penitrium Bio, emphasized, “Of the 10 million annual cancer deaths worldwide, more than 90% are ultimately caused by metastasis,” adding, “Penitrium’s ultimate goal is to create a hostile environment where cancer cells cannot survive, thereby rescuing patients from the suffering of harsh anticancer treatments and the tragic cycle of death from metastasis.”