AsianScientist (Jul. 19, 2023) –An antibody drug known as PRL3-zumab, developed by Singaporean scientists, has demonstrated a strong safety profile in Phase I trials and drug efficacy in multi-national Phase II clinical trials of late-stage cancer patients.

Results from the first-in-human Phase I study were recently published in Targeted Oncology. The clinical trial was conducted at the National University Cancer Institute, Singapore (NCIS), led by Chee Cheng Ean, Senior Consultant at NCIS, in collaboration with Intra-ImmunSG (IISG), the A*STAR spin-off biotechnology company that developed PRL3-zumab.

PRL3-zumab is a first-in-class cancer immunotherapy that binds PRL3, a protein found inside tumour cells that helps cancer to spread. Though antibodies are traditionally thought to be too large to enter a cell, pioneering research led by Zeng Qi, research director at the Institute of Molecular and Cell Biology (IMCB), A*STAR, found that PRL3 could be flipped “inside-out” onto the surface of cancer cells due to stresses from the tumour microenvironment. This phenomenon provides an opportunity for PRL3-zumab to bind PRL3 and stimulate the host immune system to kill the cancer cells, thereby inactivating the cancer-favoring functions of PRL3 and shrinking the tumor.

“It is incredibly unique that PRL3 is only specifically expressed in multiple types of cancer cells but not in normal cells. Hence, PRL3-zumab does not attack normal cells, which reduces side effects,” said Zeng, who is also the founder of IISG.

Indeed, in the Phase I trial, the team of clinicians and researchers found that PRL3-zumab was safe in late-stage cancer patients who had no other available treatments. The study’s dose-escalation (Phase Ia) cohort recruited 11 patients. These patients were treated with increasing doses of PRL3-zumab to determine if there were any side effects serious enough to prevent an increase in dosage of the treatment. The study found no such side effects and proceeded to its dose-expansion (Phase Ib) study. In this phase, the study recruited 16 patients with various tumor types, including breast, colorectal, gastric, liver, pancreatic cancer, and acute myeloid leukemia (AML), where it again found no severe drug-related side effects. The study also evaluated 24 patients for treatment efficacy and found that PRL3-zumab stabilized cancer progression in one-eighth of patients.

Following the encouraging results of the Phase I trial, PRL3-zumab is undergoing Phase II clinical trials in Singapore, USA, China, and Malaysia to further evaluate its efficacy in patients. Excitingly, a case of exceptional treatment response has emerged from the Phase II trial in the US – PRL3-zumab has extended the life expectancy of a stage 4 gastric cancer patient, a 71-year-old male, by threefold.

Furthermore, Zeng also provided additional insights on the ongoing Phase II trials. “Most of our patients have late-stage cancer with rapidly deteriorating health. Although PRL3-zumab was given at the last line of treatments, the drug still showed excellent safety and efficacy in a fair number of patients.”

With these positive findings from the clinical trials, PRL3-zumab holds promise as a potential therapy for patients with hard-to-treat cancers.

“I am excited to share that PRL3-zumab has demonstrated drug efficacy, particularly in rare aggressive diseases in ongoing trials. Since such patients have not received many treatments, their immune systems were not heavily exhausted by conventional treatments. As a first step, we are aiming for accelerated approval of PRL3-zumab to meet urgent unmet medical needs,” said Zeng.

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Source: National University Cancer Institute, Singapore ; Image: Shelly Liew/ Asian Scientist Magazine