A study of cinrebafusp alfa is underway to evaluate its safety and efficacy in combination with other therapies in patients with gastric or gastroesophageal junction cancers.
In a phase 2 study investigating treatment with cinrebafusp alfa (PRS-343) in patients with HER2-expressing gastric cancer, the first patient has been dosed with the investigational 1BB/HER2 Anticalin-based bispecific, according to a press release by Pieris Pharmaceuticals, Inc.1
“The dosing of the first patient in this next phase of development of cinrebafusp alfa marks an important milestone for patients afflicted by gastric cancer without adequate treatment options, and we look forward to further evaluating the potential of this drug," said Tim Demuth, MD, PhD, the chief medical officer of Pieris, in a press release.
The phase 2, multi-center, open-label study (NCT05190445) has a target enrollment of 80 patients. In the HER2-high patient populations, patients will be treated with cinrebafusp alfa in combination with ramucirumab (Cyramza) and paclitaxel. Patients in the HER2-low group will receive cinrebafusp alfa in combination with tucatinib (Tukysa).2
Cinrebafusp alfa treatment will be initiated at a loading dose of 18 mg/kg in weeks 1 and 3, followed by maintenance doses of 8 mg/kg twice weekly for both arms in the study.
Each arm will be evaluated for the primary end point of the objective response rate. According to the study’s protocol, the ORR must be at least 40% with meaningful durability in the HER2-low arm. In the HER2-high group, the cinrebafusp alfa combination must achieve an ORR of at least 50% with meaningful durability. The secondary end points of the study include progression-free survival, disease control rate, duration of response, time to progression, overall survival, and the number of patients with treatment-related adverse events.
Patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma who are at least 18 years old may be eligible to enroll. The key requirements include histologically or cytologically confirmed disease, an ECOG performance status of0 or 1, measurable disease per RECIST v1.1, adequate organ or hematologic function, and left ventricular ejection fraction of ≥ 50%. Any prior toxicities must be resolved for at least a grade 1 before patients can enroll in the study.
In terms of previous therapy, patients enrolling in the HER2-low arm cannot have received more than 2 prior treatment regimens for advanced disease. Those enrolling in the HER2-high arm are required to have received at least 1 prior treatment regimen for advanced disease.
The study excludes patients with disease of squamous or undifferentiated histology, central nervous system metastases, and other comorbidities and infections that may interfere with treatment in the study. In addition, patients who have had prior organ transplantation including allogeneic or autologous stem cell transplantation, an investigational agent, chemotherapy or other cancer-directed therapy within 4 weeks of study treatment initiation, radiation therapy within 4 weeks of scheduled of dosing on day 1 in the study, trastuzumab or adotrastuzumab emtansine or any other commercial or experimental drug that engages the same epitope as trastuzumab within 4 weeks of dosing in the study, and major surgery within 28 days are ineligible to enroll.
"We believe cinrebafusp alfa can provide differentiated treatment options for patients with gastric cancer via 4-1BB-mediated T-cell engagement, both in terms of efficacy and safety,” added Demuth.1
1. Pieris Pharmaceuticals announces dosing of first patient in phase 2 gastric cancer trial of 4–1BB/HER2 bispecific cinrebafusp alfa. News release. Pieris Pharmaceuticals. January 14, 2022. Accessed January 18. 2022. https://bit.ly/3qFvTld
2. Cinrebafusp Alfa in combination with ramucirumab and paclitaxel in HER2-high gastric or GEJ adenocarcinoma and in combination with tucatinib in HER2-low gastric or GEJ andenocarinoma. Clinicaltrials.gov. Accessed January 18, 2022. https://bit.ly/3Ii2C64