Oral azacitidine at a dose of 140 mg demonstrated a similar pharmacokinetic and safety profile to that of the subcutaneous formulation when administered alongside 20 mg of cedazuridine (ASTX030) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with intermediate or low body surface area (BSA), according to data from the phase 2 ASTX030-01 trial (NCT04256317).

 showed that the geometric mean ratio (GMR) for ASTX030 vs subcutaneous azacitidine was 0.913 (90% CI, 0.78-1.07; intra-coefficient of variant [CV], 39%) in the general population (n = 29), and when stratifying for BSA, the intermediate-BSA subgroup had a GMR of 0.980 (90% CI, 0.85-1.13; intra-CV, 24%), and the high-BSA subgroup had a GMR of 0.700 (90% CI, 0.55-0.89; intra-CV, 37%). Two patients had a low BSA, and both saw a GMR of over 1.0 with ASTX030. Azacitidine exposure following ASTX030 was similar on days 1, 2, and 7.

“What you see from this data is that [ASTX030] approximates around 90% of the exposure that you saw with the subcutaneous azacitidine, indicating that pharmacologically, we’re very close to the target that we wanted,” said Guillermo Garcia-Manero, MD, a professor at The University of Texas MD Anderson Cancer Center in Houston, who presented the data. “It’s worth noticing that here we saw some variations based on the BSA of the patients.”

Maximum mean percentage of long interspersed nuclear element-1 (LINE-1) demethylation was 5.95 for ASTX030 and 7.11 for subcutaneous azacitidine during cycle 1 and 5.68 and 6.37, respectively, in cycle 2. After 7-day dosing, maximum LINE-1 demethylation effect was comparable across treatment types.

“We thought that this would enable us to … proceed into the phase 3 study of this compound,” he said, noting that the phase 3 study is now underway and close to its conclusion.

A fixed-dose combination of oral azacitidine (ASTX030) and cedazuridine demonstrated a comparable total systemic exposure, pharmacodynamic profile, and clinical profile to that of subcutaneous azacitidine in patients with MDS or CMML with intermediate or low BSA.

Phase 2 data and other simulations also suggested that BSA-based dosing of the agent reduces variability of azacitidine exposure, produces a more consistent oral/subcutaneous AUC ratio regardless of body size, and could overall better optimize treatment with azacitidine. 

These data support the use of oral azacitidine as a viable alternative to subcuteanous azacitidine in clinical practice.

What were the response rates with oral azacitidine in MDS and CMML?

The overall response rate (ORR) in patients with MDS (n = 11) was 50.0%, including 5 who achieved complete response (CR) and 2 who achieved marrow complete response. Additionally, 4 patients achieved hematologic improvement (HI), including 3 erythroid, 2 neutrophil, and 3 platelet HIs. Eight patients with MDS achieved stable disease, 2 had progressive disease, and 1 was not evaluable.

No patients with CMML responded to treatment. Five had stable disease, none had progressive disease, and 1 was not evaluable. Of 2 patients with AML, 1 achieved CR, and 1 was not evaluable.

Thirteen patients were red blood cell (RBC) transfusion-dependent at baseline; of those, 30.8% achieved 8 or more weeks of RBC transfusion independence. Median overall survival (OS) had not been reached as of most recent follow-up.

ASTX030-01 is an ongoing, multicenter, randomized, open-label crossover study of single-agent oral ASTX030 or subcutaneous azacitidine, with 2 periods and 2 sequences.

Patients had MDS, CMML, other MDS/myeloproliferative neoplasms, or acute myeloid lymphoma if the patient would be considered a candidate for treatment with azacitidine monotherapy.

Enrolled patients were required to have ECOG performance statuses of 0 or 1, have adequate organ function, not have graft-versus-host disease, have a life expectancy of at least 12 weeks, and have had fewer than 2 prior cycles of a DNA methyltransferase inhibitor.

Garcia-Manero noted, however, that patients were allowed to have up to 2 prior lines of a hypomethylating agent (HMA).

Patients (n = 30) were randomized 1:1 to 1 of 2 treatment sequences. Patients in sequence A (n = 14) received ASTX030 days 1 to 7 in cycle 1, then received subcutaneous azacitidine at 75 mg/m

 in days 1 to 7 of cycle 2, and went back to ASTX030 for all remaining cycles. Sequence B (n = 16) reversed the first 2 cycles, where patients received subcutaneous azacitidine for cycle 1, then received ASTX030 for cycle 2 and all remaining cycles.

The study’s primary end point was GMR of azacitidine total cycle, confirming that dose of oral ASTX030 achieved a mean area under the plasma concentration-time curve from 0 to 24 hours (AUC

) comparable with that of subcutaneous azacitidine.

Secondary end points included clinical response rate, pharmacodynamics (LINE-1 demethylation), safety, transfusion independence, duration of response (DOR), overall survival (OS), and time to response.

No significant difference was observed between safety profiles of ASTX030 and subcutaneous azacitidine. Adverse events (AEs) were largely gastrointestinal and hematologic. The most common treatment-emergent AEs (TEAEs) were nausea (56.7%), diarrhea (50.0%), anemia (46.7%), constipation (46.7%), fatigue (46.7%), peripheral edema (30.0%), vomiting (30.0%), and thrombocytopenia (26.7%).

Any-grade AEs occurred in, including in 90.0% of patients receiving subcutaneous azacitidine in cycles 1 or 2 (n = 30), in 96.7% of patients receiving ASTX030 in cycles 1 or 2 (n = 30), in 87.5% of patients in cycle 3 or beyond (n = 24), and in 100.0% of all patients; 73.3%, 76.7%, 70.8%, and 96.7%, respectively, were related to the study drug. Grade 3 or higher AEs occurred in 60.0%, 63.3%, 54.2%, and 83.3% of patients in those groups, respectively, and 43.3%, 40.0%, 29.2%, and 63.3% were related to study drug.

Serious AEs occurred in 20.0%, 36.7%, 37.5%, and 66.7% of patients, respectively, and 3.3%, 3.3%, 4.2%, and 10.0 were related to the study drug; 2 serious AEs were fatal in patients receiving subcutaneous azacitidine in cycle 1 or 2. AEs led to study drug dose adjustment in 7 total patients. No early deaths occurred.

What were the key patient characteristics in this trial?

Garcia-Manero made note that half of all patients, including 5 receiving sequence A and 10 receiving sequence B, had intermediate BSA, defined as BSA between 1.55 and 2.15 m

. Twelve evaluable patients had high BSA, defined as at least 2.15 m

, and 2 patients had low BSA, defined as at most 1.55 m

Of note, the study included a larger BSA compared with historical demographic data in patients with MDS/AML, according to Garcia-Manero.

Further, most patients (73.3%) had MDS, and 4 patients (sequence A, 3; sequence B, 1) had received prior HMAs, and 3 patients receiving sequence B had been exposed to luspatercept.

In terms of MDS risk classification, all patients with MDS receiving sequence A (n = 11) and 54.5% of patients with MDS receiving sequence B (n = 11) had an International Prognostic Staging System-Revised score over 3.5.

All patients received at least 2 full-dose treatment cycles. The median and mean treatment durations were 3.8 months and 5.6 months, respectively (range, 1.1-13.5). Twenty-one patients discontinued treatment, including 8 who transitioned to transplant, of whom 7 had MDS and 1 had CMML, and 4 patients who had disease progression.

At the data cutoff of July 1, 2025, 9 patients remained on treatment.

Garcia-Maner G, Borate U, Brunner A, et al. A phase 2 dose confirmation trial of oral ASTX030, a combination of oral azacitidine with cedazuridine among patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. 

. 2025;146(supplement 1):491. doi:10.1182/blood-2025-491

Articles

Oral azacitidine combined with cedazuridine (ASTX030) demonstrated a comparable pharmacokinetic and safety profile to subcutaneous azacitidine in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML). The phase 2 ASTX030-01 trial showed a geometric mean ratio (GMR) close to 1.0, indicating similar drug exposure. The trial's design included a crossover study with two treatment sequences. Safety profiles were similar, with gastrointestinal and hematologic adverse events being most common. The trial's primary endpoint was met, and the phase 3 study is nearing completion.

Oral azacitidine demonstrated a similar pharmacokinetic and safety profile to the subcutaneous formulation in MDS or CMML.

Oral and Subcutaneous Azacitidine Show Comparable PK, Safety Profiles in MDS and CMML

Race Is Independent Predictive Factor for Survival in AML 

| Image credit: LELISAT - stock.adobe.com

Black patients with acute myeloid leukemia (AML) who received intensive chemotherapy in clinical trials experienced inferior overall survival (OS) and disease-free survival (DFS) benefit compared with White patients despite having similar cytogenetic profiles, indicating that Black race is an independent predictor of survival outcomes, according to findings from a 30-year retrospective analysis presented during the 

Data collected from 10 ECOG-ACRIN phase 2 and 3 trials between 1984 and 2019 revealed that Black patients experienced 31.3% greater risk of disease recurrence or death and 21.2% greater risk of death than their White counterparts.

“In this large study, we saw that Black race was an independent predictor of inferior survival in patients with AML treated on clinical trials with intensive chemotherapy, and that poorer survival of Black patients was independent of cytogenetics,” said Shella Saint Fleur-Lominy, MD, PhD, an physician at The University of Maryland School of Medicine’s Marlene and Stewart Greenebaum Comprehensive Cancer Center in Baltimore, Maryland, who presented the data.

The hazard ratio for overall survival (OS) for Black patients vs White patients was 1.212 (95% CI, 1.01-1.453; 

 = .0383), and the hazard ratio for disease-free survival (DFS) was 1.313 (95% CI, 1.05-1.641; 

 mutations were linked with poorer OS in Black patients vs White patients; Black patients with 

-mutated AML had an OS of 19.1 months compared with 8.9 months in White patients harboring 

 failed to confer favorable outcomes for Black patients, suggesting race can modify the effect of certain somatic mutations,” said Saint Fleur-Lominy.

In general, complete remission rates were similar in Black (58.2%) and White (57.5%) patients (

 = .55), 30-day mortality rates were also similar, at 7.1% and 8.9%, respectively (

 = .504). Notably, a significantly lower portion of Black patients (37.1%) underwent allogeneic stem cell transplant vs White patients (48.5%; 

 <.001). Rates of bone marrow transplant were similar in Black patients (19.0%) and White patients (20.2%; 

“Access to allogeneic transplant is a persistent inequity, even in patients with sufficient social support, to be enrolled in clinical trials,” explained Saint Fleur-Lominy.

Patients in other racial groups besides Black and White were 6% higher risk of death (HR, 1.06; 95% CI, .87-1.30) and a 14% higher risk of disease recurrence or death (HR, 1.14; 95% CI, 0.87-1.50) compared with White patients.

Did cytogenetic profiles and risk prediction differ between Black and White patients?

While European LeukemiaNet (ELN) cytogenic risk score (RS) predicted OS in Black and White patients, ELN cytogenic RS predicted DFS in White patients but not for Black patients (

OS for Black patients was 57.8 months in those with a favorable ELN cytogenic RS, 14.2 months for those with intermediate RS, and 5.8 months for those with an adverse RS. Likewise, OS for White patients with those risk profiles was 60.1 months, 15.2 months, and 7.1 months, respectively.

Complete cytogenetic profiles were available for 117 Black patients and 2162 White patients. Core binding factor AML was observed in a nonsignificantly higher percentage of Black patients (12.8%) vs White patients (8.3%).

No difference was observed for Black vs White patients in complex karyotype (CK); CK with -5/del(5q), -7/del(7q), or -17/del(17p); or AML with myelodysplasia-related changes including +8 and del(20q).

Researchers identified no racial prevalence in 

 mutations in patients with available data on these mutations (n=1218, n= 576, n = 572, and n = 683, respectively).

“There is a need for analysis of large representative AML data set with integration of ancestry, social factors, and comprehensive genomic profiling of AML,” said Fleur-Lominy, “in order to elucidate the interaction between race and outcome disparities in AML.”

What were the baseline characteristics and statistical analyses used in this study?

The study aimed to compare outcomes in Black and White patients, and categorized the patient population as Black, White, or other. The study population included 184 Black patients, 3469 White patients, and 156 other patients.

In total, Black patients comprised 1.1% to 11% of respective trial populations. Investigators identified that Black patients were significantly younger at diagnosis, having a median age of 47.9 (SD, 18.8) years vs 53.5 (SD, 16.3) years in White patients (

 <.001). Also of statistical significance, 121 Black patients (65.8%) vs 1901 White patients (54.8%) were younger than 60 (

Black and White racial groups were well-matched in gender (Female, 43.5% vs 45.6%, respectively; 

 = .595) and performance status (0 or 1, 86.4% vs 84.7%; 

Researchers used descriptive statistics to summarize baseline characteristics with the Wilcoxon rank-sum and Fisher’s exact tests. Further, multivariable Cox proportional hazards regression models were used to assess the association between race and survival outcomes adjusting for age, platelet count, white blood cell count, hemoglobin, blast percentage, ELN cytogenetic RS, and performance status. Cox models were also stratified by protocol.

Kaplan-Meier curves were used to perform subgroup analyses of OS and DFS, which were stratified by race via log-rank tests. All statistical test were 2-sided, and analysis only included patients with complete data for variables of interest.

Disclosures: Saint Fleur-Lominy disclosed his consultancy for AstraZeneca.

Saint Fleur-Lominy S, Chen L, Sun Z, et al. Inferior survival in black AML patients treated with intensive chemotherapy in ECOGACRIN clinical trials is independent of cytogenetic profiles. 

A 30-year retrospective analysis of ECOG-ACRIN trials revealed that Black patients with acute myeloid leukemia (AML) receiving intensive chemotherapy had inferior overall and disease-free survival compared to White patients, despite similar cytogenetic profiles. Black race emerged as an independent predictor of survival outcomes. NPM1 mutations were linked to poorer outcomes in Black patients, and access to allogeneic stem cell transplants was notably lower. The study highlighted the need for comprehensive genomic profiling and consideration of social factors to understand racial disparities in AML outcomes.

Findings from a retrospective analysis identified Black race as an independent predictor of inferior survival outcomes with intensive chemotherapy in AML. 

Race Is Predictive of Survival Outcomes With Intensive Chemotherapy Independent of Cytogenetics in AML

Families of pediatric patients treated with chemotherapy for acute lymphoblastic leukemia (ALL) have experienced what researchers call catastrophic financial toxicities in almost a third of their families according to data presented at the 2025 ASH Annual Meeting and Exposition.

Findings were presented during a press briefing by Daniel J. Zheng, MD, of the Division of Oncology at Children’s Hospital of Philadelphia in Pennsylvania.

Zheng stated that after children in the phase 3 DFCI 16-001 trial (NCT03020030) had received chemotherapy for 24 months, 30.0% of families had experienced household material hardship (HMH), and 31.5% of families had experienced a catastrophic income loss at some point during therapy.

“Household material hardship can be thought of as difficulty with meeting your basic living needs,” Zheng said. “So, this is most commonly explored in the dimensions of housing, food, and utilities insecurities. In this study, we measured whether families develop new HMH or catastrophic income loss, which we defined as greater than or equal to 25% of a family's annual household income.”

What was the rationale and background of the study?

Nearly a third of families of patients with pediatric ALL have catastrophic financial toxicities.

Almost a third of families of patients with pediatric ALL have also experienced catastrophic income loss during treatment of patients.

Study investigators have stressed the importance of standardizing longitudinal financial screenings for families of patients with pediatric ALL.

Pediatric ALL, Zheng stated, is the most common childhood cancer.

“And while our current cure rates are actually exceptional, successful treatment still entails more than two years of multi-agent chemotherapy, and that's a treatment paradigm that has the potential for significant financial burden for families,” he said. “Prior research has estimated an average of 200 outpatient encounters in 40 inpatient days. That's a lot of disruption to a family's day-to-day life and can result in things like direct costs of transportation and child care for other siblings, and then indirect costs like taking time off from work or even one caregiver completely quitting their job.”

DFCI 16-001 enrolled patients age 1 to 21 years with de novo B- or T-cell ALL at 8 US and Canadian centers from 2017 to 2021. Participants younger than 18 years were eligible to opt in to the correlative HMH study at the time of initial trial consent, with parents or guardians of participants completing surveys within 32 days of trial enrollment and longitudinally at 6, 12, and 24 months.

Among 422 participants — 15% of whom were Hispanic and 7% of whom were non-Hispanic Black, 23% of whom were in a single-parent household and 40% had annual household income less than 200% of the federal poverty level — with evaluable baseline survey data, 115, or 27%, reported HMH at baseline, researchers noted.

Cumulative incidence of any new HMH was 19.3% (95% CI: 15.9-23.5) at 6 months, 27.7% (95% CI: 23.8-32.4) at 12 months, and 30.0% (95% CI: 25.9-34.7) at 24 months, while the cumulative incidence of catastrophic income loss was 20.3% (95% CI: 16.7-24.7) at 6 months, 28.6% (95% CI: 24.5-33.5) at 12 months, and 31.5% (95% CI: 27.2-36.5) at 24 months, researchers reported.

Furthermore, in the subcohort of 307 families with no baseline HMH, the cumulative incidences of any new HMH or catastrophic income loss at 24 months were 24.3% (95% CI: 19.9-29.6) and 27.9% (95% CI: 23.1-33.7), respectively.

Multivariable modeling showed that children who identified as non-Hispanic Black (RR 3.5, 95% CI: 1.7-7.3), lived in a single-parent household (RR 2.1, 95% CI: 1.3-3.2), preferred a non-dominant language (i.e. non-English for U.S. participants and non-English/French for Canadian participants, RR 2.1, 95% CI: 1.2-3.6), or had baseline household income that was less than 200% of the federal poverty level (RR 1.8, 95% CI: 1.1-2.9) were more likely to develop new HMH during treatment.

In this study, researchers focused on children with newly diagnosed ALL who were enrolled in a clinical trial and followed for two years of chemotherapy, with caregivers completing surveys at four time points with questions assessing HMH and household income.

Examples of survey questions shared by Zheng included:

· Was there a time you were not able to pay the rent or mortgage on time?

· We worried whether our food would run out before we got money to buy more.

· Has the gas/electric/oil company sent you a letter threatening to shut off the gas/electricity/oil to the house for not paying bills?

“Our main finding was that a striking number of families experience new household material hardship and catastrophic income loss over the course of therapy,” Zheng said.

Regarding domains of HMH, this was predominantly driven by the development of new housing insecurity (22.2%) followed by food insecurity (15.9%), and utilities insecurity (8.6).

“And then, what's particularly notable is that one in four families who had no household material hardship at diagnosis went on to develop new household material hardship and/or catastrophic income lost by the end of chemotherapy,” Zheng said.

What are the key takeaways and next steps for the study?

One immediate takeaway from these findings, Zheng said, is that it is clinically important to standardize repeated longitudinal financial screening over the course of cancer treatment.

“So, this can't be the type of thing where you meet a family at diagnosis, they get an initial screening, and then you just assume that the family is going to be fine for the subsequent two years,” Zheng said. “Of course, this also brings up the critical need for family-centered intervention in this space.”

Zheng then highlighted that some of his co-authors on the study — Puja Umaretiya, MD, of UT Southwestern Medical Center, and Kira Bona, MD, of Dana-Farber Cancer Institute — are currently leading interventional studies exploring factors such as benefits counseling and cash transfer as potential interventions to mitigate financial toxicity.

Zheng D, Robinson E, Flamand Y, et al. Cumulative incidence of household material hardship and income loss as measures of financial toxicity during pediatric acute lymphoblastic leukemia (ALL) treatment: A report from the DFCI ALL 16-001 Trial. 

Families of pediatric patients undergoing chemotherapy for acute lymphoblastic leukemia (ALL) face significant financial challenges, with nearly a third experiencing catastrophic income loss or household material hardship (HMH). The study, conducted by Daniel J. Zheng, MD, and colleagues, highlights the financial burden of ALL treatment, which includes over two years of multi-agent chemotherapy. Factors such as race, single-parent households, language preference, and low income increase the risk of financial toxicity. The findings emphasize the need for standardized financial screening and family-centered interventions to mitigate these challenges.

Thirty percent of families of pediatric patients with ALL receiving chemotherapy experienced catastrophic financial toxicities.

Families Face Financial Hardships in Pediatric ALL


Gina Mauro is your lead editorial contact for 

. She joined the company in 2015 and has held various positions on 

; she is also the on-air correspondent for 

. Prior to joining MJH Life Sciences, she worked at Gannett as a full-time reporter with the Asbury Park Press. Email: gmauro@onclive.com 

Buparlisib plus paclitaxel failed to provide an overall survival (OS) benefit compared with paclitaxel for the treatment of patients with PD-1/PD-L1–pretreated recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), according to data from the phase 3 BURAN trial (NCT04338399).

 showed that the median OS with buparlisib plus paclitaxel was 9.6 months compared with 9.7 months with paclitaxel alone in this patient population (HR, 1.02; 95% CI, 0.83-1.26; 

“The buparlisib plus paclitaxel combination arm has a numerically higher overall response rate, but there was no increase in progression-free survival compared to the paclitaxel-only arm,” lead study author Denis Souliéres, MD, MSc, FRCPC, full professor of medicine at the Université de Montréal, Canada, said in an oral presentation during the meeting. “Translational data will permit to explore if molecular subgroups derive significant benefit.”

Buparlisib is an oral pan-PI3K inhibitor that targets all 4 isoforms of class I PI3K. Prior phase 1b data showed that buparlisib and paclitaxel showed clinical activity in patients with taxane-pretreated advanced solid tumors.

 Additionally, data from the phase 2 BERIL-1 trial showed a progression-free survival (PFS) improvement with buparlisib and paclitaxel vs placebo and paclitaxel (HR, 0.65; 

 = .65), as well as an OS improvement (HR, 0.72; 

 = .041) in patients with recurrent or metastatic squamous cell carcinoma of head and neck who experienced failure of 1 prior platinum-based therapy.

To be eligible for enrollment, patients had to have recurrent or metastatic HNSCC and have received a prior PD-1/PD-L1 inhibitor in the recurrent/metastatic setting, 1 to 2 prior lines of therapy, and an ECOG performance status of 0 or 1.

A total 487 patients were randomly assigned 2:1 between April 2021 and November 2023 to receive buparlisib at 100 mg once daily plus paclitaxel at 80 mg/m

 on days 1, 8, and 15 every 3 weeks or paclitaxel alone at the same dosage.

Stratification factors included HPV status (yes vs no). The primary end point was OS. Secondary end points were PFS, objective response rate (ORR), and duration of response (DOR) by independent radiological review committee and via investigator as per RECIST v1.1 criteria; OS, PFS, ORR, and DOR in subgroups by HPV status; safety, and patient-reported outcomes.

Most patients who discontinued the combination (98.5% for both agents) did so because of disease progression (buparlisib, 38.7%; paclitaxel, 39.9%) followed by adverse events (AEs; 38.1%; 35.6%). In the paclitaxel-alone arm, 98.8% of patients discontinued paclitaxel due to disease progression (54.9%) and AEs (17.7%).

Regarding baseline characteristics across both arms, 29.8% of patients were HPV positive, approximately half were from Europe (50.1%), and the majority were male (80.3%). The median age was 61.5 years (IQR, 56-68), and 63.4% were White; most were not Hispanic or Latino (85.6%). HPV positivity only of the oropharynx was in 19.8% of patients who received the buparlisib combination and 17.7% of those who received chemotherapy alone.

A total 42.4% and 39.0% of patients, respectively, previously received a PD-1/PD-L1 inhibitor alone or in combination with non–platinum-based therapy, while 39.3% and 45.1% of patients received the immunotherapy concurrently with platinum-based chemotherapy. A total 16.7% and 15.9% of patients received them in sequence with platinum-based chemotherapy. Furthermore, 70.0% and 68.3% of patients on buparlisib and paclitaxel alone, respectively, had metastatic disease at study entry.

Additional efficacy data showed that the confirmed ORR per IRRC was 30.3% with buparlisib/paclitaxel compared with 20.7% with paclitaxel alone (

 = .024); the unconfirmed ORRs by IRRC were 44.3% and 28.0%, respectively (

 = .0005). When assessed via investigator, the confirmed ORRs were 29.7% vs 24.4% (

 = .22) and unconfirmed ORRs were 44.6% and 28.0% (

The median DOR per IRRC was 5.6 months with buparlisib vs 9.1 months with paclitaxel alone (HR, 1.48; 95% CI, 0.89-2.44; 

 = .12); per investigator assessment, the median DOR was 7.0 months vs 6.7 months, respectively (HR, 0.97; 95% CI, 0.63-1.49; 

The median PFS per IRRC was 4.1 months in each arm (HR, 0.97; 95% CI, 0.77-1.22; 

 = .77); by investigator assessment, the median PFS was 4.3 months compared with 4.2 months, respectively (HR, 0.92; 95% CI, 0.74-1.14; 

Regarding safety, grade 3 or higher AEs occurred in 87.5% and 59.4% of patients of the combination vs paclitaxel alone arms; treatment-related grade 3 or higher AEs were reported in 71.0% and 33.8%, respectively. A total 60.1% of these AEs were related to buparlisib; 60.4% were paclitaxel related in the combination arm vs 33.8% in the monotherapy arm.

AEs that led to study drug discontinuation occurred in 45.2% and 16.9% of patients in the buparlisib combination and paclitaxel alone groups, respectively. A total 37.7% of those in the combination group were buparlisib related; on the combination arm, 35.2% were related to paclitaxel, and 16.9% were related to paclitaxel on the monotherapy arm. AEs of special interest occurred in 88.2% and 75.0% of patients, respectively.

Souliéres noted that there were no characteristics that were a factor in OS improvement with the combination vs paclitaxel alone, except for a potential survival advantage in patients with HPV-positive oropharynx cancer (HR, 0.73; 95% CI, 0.46-1.17) vs other HPV status and primary site of cancer (HR, 1.09; 95% CI, 0.86-1.37). North American patients also had a significantly higher OS advantage with buparlisib/paclitaxel (HR, 0.46; 95% CI, 0.29-0.73) compared with Asian Pacific patients (HR, 1.05; 95% CI, 0.73-1.52) and European patients (HR, 1.39; 95% CI, 1.02-1.89).

“There were more HPV-positive patients that were North American patients compared to what we saw in Asia and Europe, but I will remind you that the HPV positivity did not specifically translate into an OS in the overall analysis,” Souliéres commented.

Souliéres concluded that the immunotherapy-refractory HNSCC patient population remains one with significant unmet need.

Disclosures: Souliéres cited research funding to institution from MSD, EMD-Serono, AZ, BMS, ANL, Pfizer, Incyte, Eisai, GSK, Novartis, and ROTG; compensated work for advisory or consultant roles with ANL, Bicara, Novartis, MSD, EMD-Serono, Roche/Genentech, Ipsen, Eisai, BMS, Pfizer, OpenAI, Siemens, Canadian Cancer Society; uncompensated work with HNCIG.

SouliéresD, et al. BURAN: A phase III study of buparlisib (BUP) plus paclitaxel (PAC) in patients with PD-1(PD-L1)-pretreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA48.

Zambrano Cruz C, Schuler MH, Machiels J-PH, et al. Phase lb study of buparlisib (BKM120) plus either paclitaxel (PTX) in advanced solid tumors (aST) or PTX plus trastuzumab (TZ) in HER2+ breast cancer (BC).

. 2014;32(15 suppl):627. doi:10.1200/jco.2014.32.15_suppl.627

SouliéresD, Faivre S, Mesía R, et al. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. 

. 2017;18(3):323-335. doi:10.1016/S1470-2045(17)30064-5

The phase 3 BURAN trial evaluated buparlisib plus paclitaxel versus paclitaxel alone in PD-1/PD-L1-pretreated recurrent/metastatic HNSCC patients, showing no overall survival benefit. Median overall survival was similar between the two groups, and progression-free survival did not improve with the combination. Although the combination had a higher overall response rate, it was associated with more adverse events. Subgroup analysis suggested potential benefits in HPV-positive oropharynx cancer and North American patients. The study highlights the unmet need in immunotherapy-refractory HNSCC, despite the lack of significant survival improvement.

Buparlisib plus paclitaxel did not show an improvement in OS vs paclitaxel alone in PD-1/PD-L1–pretreated recurrent/metastatic HNSCC.

Buparlisib Plus Paclitaxel Fails to Yield OS Benefit in PD-1/PD-L1–Pretreated HNSCC

Zabilugene almadenorepvec plus SOC in untreated metastatic PDAC:

Image by Ashling Wahner & MJH Life Sciences Using AI

Zabilugene almadenorepvec (VCN-01) in combination with standard-of-care (SOC) gemcitabine plus nab-paclitaxel (Abraxane) led to benefits in terms of overall survival (OS), progression-free survival (PFS), and duration of response (DOR) vs SOC alone for the treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received no previous systemic therapy, according to data from the phase 2b VIRAGE trial (NCT05673811) presented during the 

Results from the multicenter, open-label, randomized study presented by Rocio Garcia-Carbonero, MD, head of the GI and NET oncology unit of Hospital Universitario 12 de Octubre’s oncology department, in Madrid, Spain, confirm that the trial met its primary end points of OS and safety along with secondary end points of PFS, response rates, DOR, and biomarker Ca19.9.

“Survival benefit was greater among patients who received 2 VCN-01 doses and with longer follow-up,” explained Garcia-Carbonero in her presentation. “These encouraging data support further evaluation of this combination in a larger, blinded, randomized trial with additional VCN-01 doses.”

How effective was VCN-01 in metastatic PDAC?

A preplanned subgroup analysis of all patients who started the fourth cycle of SOC—which, for patients in the experimental arm included 2 doses of VCN-01—revealed that risk of death was reduced by 56% for patients who received VCN-01 and SOC compared with SOC alone, with an improved OS of 14.8 months (95% CI, 10.6-NE) vs 11.6 months (95% CI, 8.6-12.8) in the SOC-alone arm (HR, 0.44; 95% CI, 0.21-0.92; 

Likewise, the subgroup analysis showed the addition of VCN-01 led to a 52% reduction in the risk of disease progression or death compared with the SOC arm; patients receiving VCN-01 demonstrated a PFS of 11.2 months (95% CI, 7.3-16.6) vs 7.4 months (95% CI, 5.7-8.4) in patients receiving SOC alone (HR, 0.48; 95% CI, 0.25-0.91; 

Median OS in the modified intent-to-treat (mITT) population was 10.6 months (95% CI, 6.6-14.8) vs 8.6 months (95% CI, 6.9-11.6) in the VCN-01 and SOC arms, respectively, with an HR of 0.69 (95% CI, 0.42-1.12; 

 = .196). The full analysis set (FAS) population yielded a median OS of 10.8 months (95% CI, 7.4-15.8) vs 8.6 months (95% CI, 6.9-11.6), respectively, with an HR of 0.5 (95% CI, 0.34-0.96; 

Patients receiving VCN-01 had a median DOR of 11.2 months (95% CI, 7.4-NE) vs 5.4 months (95% CI, 2.06-6.8) in the SOC arm (HR, 0.22; 95% CI, 0.08-0.62; 

The VCN-01 arm had an overall response rate (ORR) ORR of 39.6% with 1 complete response, 18 partial responses, 18 patients with stable disease, and 11 patients with progressive disease; the SOC alone arm yielded a 31.3% ORR with no complete responses, 15 partial responses, 19 patients with stable disease, and 14 patients with progressive disease (

 = .314). Disease control rates (DCR) were 77.1% and 70.8% for experimental and SOC arms, respectively.

Additional biologic data confirmed the efficacy of VCN-01.

“Sustained VCN-01 genomes levels indicated persistent replication and confirmed the bioactivity of the second dose despite the presence of neutralizing antibodies,” Gracia-Carbonero reported in her presentation.

How safe was VCN-01 in this patient population?

All serious treatment-related adverse events (TRAEs), of which there were 13, were resolved. The most common grade 3 or higher TRAEs were transaminase increase (15.1%), flu-like symptoms (13.2%), and drug-induced liver injury (3.8%). TRAEs decreased with the second dose, with only 1 patient experiencing a grade 3 or higher TRAE (asthenia/fatigue) compared with 27 in the first dose.

Two patients died of treatment-emergent AEs (TEAEs), but neither were related to VCN-01 or SOC. The VCN-01 arm had greater incidence of grade 3 or higher neutropenia (33.9% vs 14.6%), increased transaminase (20.8% vs 10.4%), and increased GGT (7.5% vs 0%), among others TEAEs.

VCN-01: What Is It, and how was it dosed?

VCN-01 is an oncolytic adenovirus which multiplies in cancer cells with a dysfunctional RB1 pathway, according to Garcia-Carbonero. VCN-01 then expresses hyaluronidase (PH2) and degrades tumor stroma, encouraging chemotherapy efficacy and anticancer immune response.

The systemic treatment brings VCN-01 to the primary tumor as well as metastases while de-targeting the liver. It is designed to target tumor cells while leaving healthy tissue intact, making “cold” tumors “hot” and priming them for immunotherapy.

Patients in the VIRAGE trial were randomized 1:1 to receive either SOC, which entails 125 mg/m

 of IV nab-paclitaxel days 1, 8, and 15 of 28-day cycles, or SOC with 2 doses of IV VCN-01 (1x10

 vp) a week before cycles 1 and 4 of SOC therapy. Each arm contained 46 patients.

Patients eligible for VIRAGE had histologically or cytologically confirmed newly diagnosed mPDAC with no prior systemic therapy and had an ECOG status of 0 or 1. Stratification factors included geographical area (US vs EU) and ECOG status (0 vs 1). OS was analyzed after 57 total deaths.

Cid RAP, Mercade TM, Laquente B, et al. VIRAGE trial: Randomized phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 2216MO.

The combination of zabilugene almadenorepvec (VCN-01) with standard gemcitabine and nab-paclitaxel showed improved outcomes in metastatic pancreatic ductal adenocarcinoma (mPDAC) patients, as per the phase 2b VIRAGE trial. The study demonstrated significant enhancements in overall survival (OS), progression-free survival (PFS), and duration of response (DOR) compared to standard care alone. VCN-01, an oncolytic adenovirus, targets cancer cells with a dysfunctional RB1 pathway, enhancing chemotherapy efficacy. The trial confirmed the safety and efficacy of VCN-01, with manageable adverse events and promising biological activity.

Zabilugene almadenorepvec plus SOC therapy was active in patients with treatment-naive metasatic PDAC.

Bridget Hoyt

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