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As David Andorsky, MD, explains, the treatment landscape of chronic myeloid leukemia (CML) has changed significantly since the approval of imatinib (Gleevec), the first of 6 approved tyrosine kinase inhibitors (TKIs).

“The treatment of CML has really dramatically changed over the past 15 or 20 years, with the advent of the tyrosine kinase inhibitors,” Andorsky, medical oncologist at Rocky Mountain Cancer Centers said in an interview with Targeted Oncology.

Asciminib (Scemblix) is another TKI, approved by the FDA for the treatment of Philadelphia chromosome-positive CML in chronic phase (CML-CP) in October 2024.¹ Unlike other TKIs that bind to the ATP pocket of the BCR::ABL protein, asciminib binds to a different site called the myristoyl binding pocket. This unique binding mechanism may contribute to its distinct side effect profile and its ability to overcome certain resistance mutations, such as the T315I mutation, which most other TKIs are not active against.

The ASC2ESCALATE trial (NCT05384587) is a phase 2, single-arm, open-label study designed to assess the efficacy and safety of asciminib in adult patients with CML-CP.² The trial includes 2 cohorts: newly diagnosed (1L) patients and patients who had previously received 1 TKI (2L). An interim analysis specifically focused on the 2L cohort, which included patients who had discontinued their prior TKI due to insufficient efficacy or intolerance.

In the 2L cohort of the ASC2ESCALATE trial, patients initially received asciminib 80 mg once daily (QD). However, Andorsky noted that the unique aspect of the study design was the inclusion of dose escalation points. If a patient’s BCR::ABL1IS level was greater than 1% at week 24, their dose was increased to 200 mg QD. A further escalation was possible at week 48 if the BCR::ABL1IS level was still greater than 0.1%, either from 80 mg to 200 mg QD or from 200 mg QD to 200 mg twice daily. Patients experiencing significant grade 3/4 or persistent grade 2 toxicity were not eligible for dose escalation.

The interim analysis, including 63 patients evaluable for week 24 efficacy, showed high molecular response rates. At week 24, 82.5% of patients had a BCR::ABL1IS level less than 1%. The primary end point, major molecular response (MMR), was achieved by 44.4% of patients. Deeper molecular responses were also observed, with 25.4% achieving MR4 and 9.5% achieving MR4.5 at this early time point.

Regarding safety and toxicity, Andorsky noted that asciminib was generally well-tolerated. “In general, most of the adverse events [AEs] we saw were low grade. Grade 3 or higher AEs that were common were hypertension, which was seen about 8.9% of patients, thrombocytopenia seen in 6.9%, and neutropenia seen in 5.9%.”

The most common all-grade AEs (occurring in 20% or more of patients) were headache (22.8%) and nausea (20.8%). Overall, AEs led to dose adjustment/interruption in 26.7% of patients and discontinuation in only 4 patients (4.0%), with 2 of 3 discontinuations due to grade 2 but bothersome AEs. No arterial-occlusive events or on-treatment deaths were reported.

Patients in the 2L cohort had discontinued their prior TKI treatment due to either lack of efficacy (56.4% of patients) or intolerance (43.6% of patients). This indicates that asciminib is being evaluated in a population where previous TKI options were no longer suitable, highlighting its potential as a valuable second-line treatment option.

Future research will focus on longer follow-up to assess the durability of responses and the long-term tolerability of asciminib.

“For this particular study, I think what we’re looking for is longer follow-up,” Andorsky said. “How durable are these responses? How tolerable is the drug in the long term? Do we see higher incidence of side effects or treatment discontinuation?”

Another critical question is the effectiveness of the dose escalation strategy in allowing patients with suboptimal responses to remain on the same medication.

“I also think we really want to see what happens with the patients that do have the dose escalation. Is that an effective strategy to keep patients on the same medication, or are those patients are going to have to switch to a different TKI?” Andorsky asked.

Additionally, larger phase 3 trials comparing asciminib to other TKIs in the first-line setting, which will help to determine asciminib’s optimal position within the broader CML treatment landscape based on its efficacy and safety profile compared to existing options.

Based on current understanding, asciminib is considered an effective drug for many patients, and there are no specific biomarkers or known resistance mutations that would necessarily lead to its avoidance, except for the T315I mutation, against which asciminib is active. The toxicities of TKIs can be idiosyncratic, making it difficult to predict individual AEs. Therefore, at present, it’s not a matter of whether a patient should avoid asciminib, but rather where it fits into their individualized treatment plan given its efficacy and unique safety profile.

REFERENCES:

1. FDA grants accelerated approval to asciminib for newly diagnosed chronic myeloid leukemia. News release. FDA. October 29, 2024. Accessed August 15, 2025. https://tinyurl.com/4xe45e3n

2. Andorsky DJ, Luskin MR, Tantravahi SK, et al. Efficacy and safety of asciminib (ASC) in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI): Interim analysis (IA) of the phase 2 ASC2ESCALATE trial. J Clin Oncol. 43, 6516-6516(2025).DOI:10.1200/JCO.2025.43.16_suppl.6516

A recently published study of more than 25,000 patients with migraine showed that cardiovascular events (CV) occurred slightly more in patients on triptans than not; however, a multivariable analysis revealed no significant association between triptan use and increased CV events. Overall, this study reinforced the safety of triptans to treat migraine, and further highlighted the importance of considering individual risk factors when prescribing triptans.¹

Published in Migraine, the retrospective study conducted in southern Israel analyzed electronic medical records from January 2000 to 2022 for 26,054 patients with migraine, 12,560 (48.2%) of whom initiated triptan therapy. At baseline, the prevalence of CV risk factors including dyslipidemia, diabetes mellitus, hypertension, smoking, atrial fibrillation, and obesity were higher in the non-triptan group (standardized mean difference [SMD] = 0.028-0.289).

When comparing the groups, the prevalence of CV events, including myocardial infarction and ischemic stroke, was slightly higher in the triptan group (5.1%) compared with the non-triptan group (4.1%; SMD = 0.047). Of note, medication usage, including acetylsalicylic acid, anticoagulants, antiplatelets, statins, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, was also higher in the non-triptan group coming into the study (SMD = 0.023-0.105).

“Triptans remain contraindicated in patients with prior myocardial infarction, stroke, or uncontrolled hypertension, and our study does not suggest that triptans are safe in those specific populations,” lead author Ido Peles, MD, PhD, team lead of Medical Data Analysis at the Soroka Medical Center, Ben-Gurion University of the Negev, and colleagues, wrote. “The distinction between contraindications and general CV risk factors is critical, as overestimating risk could lead to unnecessary avoidance of triptans in patients who might otherwise benefit from effective migraine treatment.”

A small subset of patients in the triptan group, 0.3% (n = 33), experienced a subsequent CV event within 90 days from triptans; however, this group had a higher prevalence of CV risk factors (SMD = 2.624). Additionally, patients with migraine with subsequent CV events were more likely to have used triptans more frequently, with 81.8% using triptans more than once compared with 51.0% in the non-CV group (SMD = 1.366). In addition, the mean number of triptan pills per month was significantly higher in the CV event group (2.8 vs 1.9 pills/month; SMD = 0.328).

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In terms of triptan usage patterns, the mean age at initiation was 40.5 (SD, 14.2) years, with most patients (89.5%) using 1-4 pills/month. Sumatriptan, found in 36.3% of triptan-treated patients, was the most common, followed by rizatriptan (30.4%) and eletriptan (28.2%). A small portion of patients (14.0%) used 5-9 pills/month, and an even smaller portion (9.2%) used at least 10 pills, indicative of medication overuse.

An exposure-outcome association analysis using a multivariable weighted mixed-effects survival regression model adjusted for demographic variables and CV risk factors, such as hypertension, diabetes, smoking, dyslipidemia, and obesity. All told, results revealed that the use of triptans in the 3 months prior to the CV event was not significantly associated with an increased hazard for these events (adjusted HR [aHR], 0.96; 95% CI, 0.77-1.23).

Several different sensitivity analyses showed that (A) both 1 month (aHR, 0.84; 95% CI, 0.68-1.06) and 6 months (aHR, 0.83; 95% CI, 0.67-1.05) post-triptan purchase and (B) whether the patients took triptans only once (aHR, 0.99; 95% CI, 0.69-1.15) or more than once (aHR, 1.02; 95% CI, 0.83-1.29) had no significant risk on CV events. Similarly, specific type of triptan (aHR, 0.79-1.07) and the monthly mean number of triptans taken had no statistically significant risk of CV events, further reinforcing the primary findings.

“These findings may provide reassurance to clinicians and ease concerns regarding the CV safety of triptans for patients with CV risk factors, where no formal contraindication exists,” Peles et al concluded. “Nevertheless, it is essential for clinicians to carefully evaluate individualized patient profiles when prescribing triptans to patients with migraine, including monitoring of high-frequency users, particularly for patients with underlying or emerging CV risks.”

REFERENCE
1. Poles I, Shneyour RS, Levanon E, et al. Cardiovascular risk and triptan usage among patients with migraine. Migraine. 2025;65(7):1095-1106. doi:10.1111/head.14968

An experimental cancer vaccine has shown promise in keeping certain cancers from coming back.

In a phase 1 clinical trial led in part by the UCLA Health Jonsson Comprehensive Cancer Center, researchers tested the vaccine (ELI-002 2P) with 25 patients who had been treated for pancreatic and colorectal cancer.

The patients had all undergone surgery to remove tumors and showed “signs of minimal residual disease” or traces of DNA, putting them at a high risk of recurrence, according to a UCLA press release.

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More than 80% of pancreatic cancer patients experience recurrence of the disease after surgery, research shows — and for 40% to 50%, this happens within the first year.

For colorectal cancer, the recurrence rate is between 30% and 50% and is most likely to occur within the first two years after surgery.

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Mutations in the KRAS gene are responsible for half of colorectal cancers and more than 90% of pancreatic cancers. The vaccine, which targets those mutations, was given via a series of injections to activate an immune response in the lymph nodes.

A majority (21 out of 25) of the patients generated “KRAS-specific T cells,” which indicates a stronger immune response. The ones with higher T-cell responses showed a longer relapse-free survival compared to those with lower responses, the researchers found.

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For three colorectal cancer patients and three pancreatic cancer patients, the vaccine appeared to remove all disease biomarkers.

Among the patients who showed the strongest immune response, a majority were still cancer-free nearly 20 months after receiving the vaccine.

The findings were published in Nature Medicine.

“This is an exciting advance for patients with KRAS-driven cancers, particularly pancreatic cancer, where recurrence after standard treatment is almost a given and effective therapies are limited,” said first author of the study, Zev Wainberg, M.D., professor of medicine at the David Geffen School of Medicine at UCLA and researcher in the UCLA Health Jonsson Comprehensive Cancer Center, in the release.

“We observed that patients who developed strong immune responses to the vaccine remained disease-free and survived for much longer than expected.”

In another finding, 67% of the patients in the trial showed immune responses to “additional tumor-associated mutations,” indicating that the vaccine could be used to suppress “broader anti-tumor activity.”

One of the benefits of ELI-002 2P, according to the researchers, is that it’s considered “off-the-shelf,” which means it’s a mass-produced, standardized vaccine that doesn’t have to be personalized for each individual patient.

“This study shows that the ELI-002 2P vaccine can safely and effectively train the immune system to recognize and fight cancer-driving mutations,” Wainberg said.

“It offers a promising approach to generating precise and durable immune responses without the complexity or cost of fully personalized vaccines.”

The team has already finished enrolling participants for a phase 2 study that will test ELI-002 7P, the next iteration of the vaccine that will target a “broader set” of KRAS mutations, the release stated.

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The study was sponsored and funded by Elicio Therapeutics, the Massachusetts company that developed the vaccine.

It was conducted in conjunction with the MD Anderson Cancer Center and the Memorial Sloan Kettering Cancer Center.

Dr. Marc Siegel, Fox News senior medical analyst, was not involved in the study but commented that targeted therapies are becoming increasingly important tools in the fight against cancer.

“Solid tumors, especially pancreatic, can be difficult to treat because they are not as mutagenic (capable of inducing or causing mutations) as hematological malignancies (blood cancers) or melanoma, for example, so they don’t have as many ready targets for immunotherapy,” he told Fox News Digital.

For more Health articles, visit www.foxnews.com/health

“The new cancer vaccine from UCLA is very promising as a major tool against these cancers, as it ‘programs’ the immune system to target these mutations and has been shown in the NATURE study to elicit a strong clinical response.”

Original article source: Cancer vaccine shows promise in preventing recurrence of pancreatic, colorectal tumors