Natural killer (NK) cells engineered with interleukin (IL)-21 have shown promising results in targeting glioblastoma (GBM), while Merck's pembrolizumab trials for non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma (cSCC) have been halted. Additionally, NXP800 received orphan drug designation for ARID1a-deficient ovarian cancers, and a phase 3 trial has commenced for BAY 2927088 in HER2-mutant NSCLC.
IL-21 Enhances NK Cell Cytotoxicity in Glioblastoma
Research led by Mayra Shanley, MD, at The University of Texas MD Anderson Cancer Center, evaluated the efficacy of NK cells expressing either IL-15 or IL-21 in targeting GBM. The findings indicated that IL-21 NK cells outperformed IL-15 NK cells in safety and long-term tumor control. "We chose to engineer NK cells with IL-21 because we observed that cytokines have the potential to enhance NK cell cytotoxicity," Shanley explained. "IL-21 was particularly effective in maintaining the long-term cytotoxicity of NK cells."
Previous work had shown that glioblastomas are highly susceptible to NK cell-mediated killing. However, NK cells exposed to increasing numbers of tumor cells gradually became dysfunctional. IL-21 addressed this challenge by preventing dysfunction and enabling NK cells to sustain their cytotoxicity over an extended period.
Pembrolizumab Trials Halted
Merck has halted the phase 3 KEYNOTE-867 and KEYNOTE-630 trials of pembrolizumab (Keytruda) based on recommendations from an independent data monitoring committee. The decision was made after reviewing data from a planned interim analysis, which showed that pembrolizumab combined with stereotactic body radiotherapy (SBRT) did not improve event-free survival or overall survival.
The KEYNOTE-867 trial compared pembrolizumab with SBRT for stage I or II NSCLC. The KEYNOTE-630 trial evaluated pembrolizumab for treating high-risk, locally advanced cSCC following surgery and radiation.
NXP800 Receives Orphan Drug Designation
NXP800 has been granted orphan drug designation by the FDA for the potential treatment of patients with ARID1a-deficient ovarian, fallopian tube, and primary peritoneal cancers. This agent targets the HSF1 pathway and has demonstrated strong antitumor effects in ARID1a-mutated ovarian carcinoma and other disease models. Phase 1a of the study is the first-in-human clinical trial of NXP800, with 18 patients having received at least 1 dose of the agent as of April 2023.
"In ovarian cancer it has been uncommon to receive this designation for the treatment of a subset of the disease. We therefore believe that this orphan drug designation granted by the FDA for NXP800 for the treatment of a subset of ovarian cancer, specifically for patients with an ARID1a deficiency, provides further validation for NXP800's mechanism of action and the target patient population in our ongoing phase 1b clinical trial in patients with platinum-resistant, ARID1a-mutated ovarian cancer," said Ron Bentsur, MBA, chairman and chief executive officer of Nuvectis.
BAY 2927088 in HER2-Mutant NSCLC
Enrollment has begun for the phase 3 SOHO-02 trial (NCT06452277), which is evaluating the safety and efficacy of BAY 2927088 vs the current standard of care. The first patient with advanced NSCLC and a tumor that has activating HER2 mutations has been enrolled for frontline treatment. BAY 2927088 is a reversible tyrosine kinase inhibitor that targets mutant HER2, including HER2 exon 20 insertions and point mutations, and inhibits EGFR with high selectivity for mutant forms over wild-type EGFR.
"Our commitment to precision medicine is not just a promise but a mission to address the critical unmet needs of individuals battling HER2-mutant NSCLC, a variant of the most prevalent form of lung cancer," said Christian Rommel, PhD, head of research and development at Bayer’s pharmaceuticals division. "By advancing innovative research, we are dedicated to improving survival rates for those affected by this devastating disease."
