HiberCell to Present Preliminary Results from the Phase 1b Trial of GCN2 Activator HC-7366 when Combined with WELIREG® (belzutifan) for the Treatment of Late-Line Clear Cell Renal Cell Carcinoma (ccRCC) at the Upcoming 2026 ASCO Annual Meeting
- Data from Phase 1b dose escalation and expansion trial (n=69) shows a favorable safety profile, with manageable adverse events consistent with the known profiles of the respective drugs.
- Encouraging preliminary signals of efficacy for the higher dose combination cohorts of HC-7366 with belzutifan were observed. Additionally, several patients in the dose escalation and initial expansion (Expansion 1) remain on treatment.
- Translational analyses demonstrate clear evidence of HC-7366 pathway engagement and a pharmacodynamic profile differentiating the combination from the known effects of HC-7366 and belzutifan monotherapy.
- Second Dose Expansion Cohort (Expansion 2) fully enrolled, with updated results from both Expansion 1 and Expansion 2 expected in 2H 2026 and full results to be reported at a future date.
ROSEVILLE, Minn., May 21, 2026 (GLOBE NEWSWIRE) -- HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics targeting the integrated stress response (ISR) to address cancer relapse, metastasis, and resistance, today announced that preliminary results from its ongoing Phase 1b study (NCT06234605) of HC-7366 in combination with WELIREG® (belzutifan), Merck’s (known as MSD outside of the United States and Canada) oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, will be presented in two poster presentations at the upcoming 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The study is evaluating HC-7366, an activator of the ISR kinase GCN2, in patients with advanced clear cell renal cell carcinoma (ccRCC) whose disease progressed after prior PD-1/PD-L1 checkpoint inhibitor and VEGF-tyrosine kinase inhibitor (VEGF-TKI) therapy.
"These preliminary results from the Phase 1b study are encouraging,” said Robert Motzer, M.D., lead principal investigator for the study. “In a patient population with limited treatment options following checkpoint inhibitor and VEGF-TKI therapy, the combination of HC-7366 and belzutifan demonstrated a manageable safety profile and early signals of disease control that warrant further investigation.”
“The data from our dose escalation and expansion cohorts suggest that HC-7366 in combination with belzutifan is generally well tolerated, with preliminary efficacy findings that are consistent with our preclinical hypotheses,” said Nandita Bose, Ph.D., Chief Development Officer of HiberCell. “While these are early results, the observed response rates and pharmacodynamic evidence of pathway engagement provide a reasonable basis for continuing evaluation in our Expansion 2 cohort."
Abstract 4534 - A phase 1b, open-label, safety, tolerability, and efficacy study of HC-7366 in combination with belzutifan in patients with locally advanced (inoperable) or metastatic renal cell carcinoma.
The study enrolled patients with advanced ccRCC previously treated with ≥1 anti-PD-1/PD-L1 and ≥1 VEGF-TKI. As of the later data cutoff date for the poster presentation, April 23, 2026, 69 patients received study treatment: 16 monotherapy and 53 as part of dose escalation/Expansion 1 of HC-7366 in combination with belzutifan (7 at 20 mg, 22 at 40 mg, 24 at 60 mg with 120 mg belzutifan). Expansion 2 in ~20 patients is fully enrolled and follow-up is ongoing.
The median number of prior therapies was 3 (range 1-5) in monotherapy and 2 (range 1-4) in combination. Most TEAEs were Grade 1-2. Grade 3 events were mainly hematological (anemia) and gastrointestinal (nausea and diarrhea), with one DLT (Grade 3 nausea, 40 mg combination).
In efficacy-evaluable patients, the 40 mg combination (median follow-up of 13.3 months) demonstrated a best overall response rate (BORR) of 37%, including a confirmed ORR (cORR) of 26%, disease control rate (DCR) of 89%, and primary progressive disease (PD) rate of 11%. The 60 mg combination (median follow-up of 10.9 months) had a BORR and cORR of 37%, DCR of 84%, and primary PD rate of 16%. In monotherapy, BORR of 15% and DCR of 62% were observed. Early efficacy signals at 40–60 mg align with the preclinical projected optimal efficacious dose range.
Overall, HC-7366, alone or in combination with belzutifan, was generally well tolerated. Preliminary efficacy analyses indicate favorable disease control, characterized by a high DCR and low primary PD for the combination.
Abstract 4535 - Combining HC-7366 with belzutifan in patients with renal cell carcinoma to alter tumor and microenvironment: Pharmacokinetic and pharmacodynamic (PK/PD) analysis of a phase 1b study.
Findings from a robust translational program, including pharmacokinetic and pharmacodynamic analyses from paired tumor biopsies and systemic biomarker assessments, demonstrated clear evidence of HC-7366 pathway engagement and a differential pharmacodynamic biomarker profile distinguishing monotherapy from the combination. Notably, several favorable changes countering ccRCC biology were observed, including sustained inhibition of the HIF-2 target EPO, reduction of HIF-1α, cell cycle inhibition, and modulation of pro- and anti-tumor adipokines. Modulation of angiogenic and immune-related pathways further supports the scientific rationale for evaluating HC-7366/belzutifan in combination with immune checkpoint inhibitors and/or VEGF-TKIs.
WELIREG® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
About HC-7366
HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have antitumor and immunomodulatory activity as a monotherapy and in combination with various standard-of-care agents in preclinical models of both solid and liquid tumors. HC-7366 is currently under clinical development in Phase 1b studies in ccRCC and acute myeloid leukemia (AML).
About HiberCell
HiberCell is a clinical-stage oncology company, dedicated to the advancement of first-in-class agents with the novel mechanism of action of modulation of adaptive stress pathways. We believe that therapeutic modulation of these mechanisms allows us to address tumor metastasis, treatment resistance, and cancer relapse, all significant drivers of cancer-related deaths. Our GCN2 activator, HC-7366, is currently under investigation in Phase 1b trials in ccRCC and AML. Meanwhile, our PERK inhibitor, HC-5404, is advancing into Phase 1b development. For more information about HiberCell, please visit hibercell.com.
Dr. Motzer has financial interests related to Merck.
For Media/Investor Inquiries:
IR@hibercell.com
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