The Targeted Pulse: IL-21 Promises to Revolutionize Treatment for Glioblastoma, Pembrolizumab Trials Halted in Lung and Skin Cancer, and More

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Exploring IL-21’s Potential to Transform Glioblastoma Treatment with NK Cells

Researcher Mayra Shanley, MD, and team set out to evaluate the efficacy of natural killer (NK) cells expressing either interleukin (IL)-15 or IL-21 in targeting glioblastoma (GBM). Their findings showed that IL-21 NK cells outperformed IL-15 NK cells in terms of safety and long-term tumor control, suggesting a potentially promising treatment option for GBM. In contrast, IL-15 NK cells were more toxic when administered directly to the tumor site.

“We chose to engineer NK cells with IL-21 because we observed that cytokines have the potential to enhance NK cell cytotoxicity,” Shanley explained. “We observed that IL-21 was particularly effective in maintaining the long-term cytotoxicity of NK cells. Our previous work had shown that glioblastomas are highly susceptible to NK cell-mediated killing. However, when NK cells were exposed to increasing numbers of tumor cells, they gradually became dysfunctional. IL-21 addressed this challenge by preventing dysfunction and enabling NK cells to sustain their cytotoxicity over an extended period,” she told Targeted Oncology^TM in an interview. Shanley is a principal research scientist at The University of Texas MD Anderson Cancer Center.

KEYNOTE Trials Evaluating Pembrolizumab in Skin and Lung Cancer Halted

Merck has halted the phase 3 KEYNOTE-867 (NCT03924869) and KEYNOTE-630 (NCT03833167) 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.

In the KEYNOTE-867 trial, investigators compared pembrolizumab with SBRT for the treatment of stage I or II non–small cell lung cancer (NSCLC). Investigators in the KEYNOTE-630 trial evaluated pembrolizumab for treating high-risk, locally advanced cutaneous squamous cell carcinoma (cSCC) following surgery and radiation.

“Our understanding of cancer and how it can be treated has rapidly evolved in recent years, but unmet needs remain across different types of cancer and stages of disease,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a press release. “That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet need, such as NSCLC and cSCC, with the goal to help even more patients. We are extremely grateful to all of the patients, caregivers and investigators for their participation in these studies.”

MonumenTAL-1 Trial Reveals Exciting Potential of Talquetamab

At a Case-Based Roundtable® event, Tara K. Gregory, MD, offered compelling insights into the data from the MonumenTAL-1 trial (NCT03399799/NCT04634552), which evaluated talquetamab (Talvey) in patients with relapsed/refractory multiple myeloma. Gregory explained that the MonumenTAL-1 study enrolled patients with high-risk features seen in the real world, and that reduction of the dose improved some toxicities and maintained efficacy on the trial.

“Talquetamab was [investigated in] the MonumenTAL-1 study, and there was a phase 1 and phase 2 component,” Gregory explained. “What I think is fantastic about the study is that first they are trying to figure out their dosing schema. Do you have a smaller dose every week, or do you go every other week? … They also had these patients profiled [based on whether] they had seen anti B-cell maturation antigen therapy before.”

Targeting a Rare Ovarian Cancer, NXP800 Shows Promise in Clinical Trials

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 agentworks by targeting the HSF1 pathway andhas 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,” Ron Bentsur, MBA, chairman and chief executive officer of Nuvectis, said in a press release.

BAY 2927088 Takes Aim at HER2-Mutant NSCLC in New Phase 3 Study

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 areversible 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, in a press release. “By advancing innovative research, we are dedicated to improving survival rates for those affected by this devastating disease. This endeavor underscores our commitment to pioneering precise and personalized healthcare solutions for those in direct need.”

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.

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