Megan Hollasch

1.34 mg of Fotivda provided decreased tumor size and may be more tolerable than an 0.89-mg dose in RCC: © Axel Kock - stock.adobe.com

Among patients with renal cell carcinoma (RCC), the Food and Drug Administration (FDA)-approved starting dose of 1.34 milligrams (mg) of Fotivda (tivozanib) resulted in greater antitumor activity than a reduced dose of 0.89 mg, while incidence of hypertension were seen to be comparable.

Progression-free survival: The time a patient lives without their disease spreading or worsening.

Best overall response: The best response a patient has to treatment.

Overall survival: The time a patient lives, regardless of disease status.

This was according to results from an integrated efficacy and safety exposure response analysis that included the phase 3 TIVO-1, 

 studies presented at the 2025 ASCO Genitourinary Cancers Symposium.

“[There was a] strong exposure response relationship between cycle 2 [Fotivda] serum [exposures] and progression-free survival [PFS],” Dr. Bradley McGregor, lead study author, wrote in a poster presentation of the data. McGregor is director of Clinical Research for the Lank Center of Genitourinary Oncology, a senior physician as well as Marra Lochiatto Investigator at Dana-Farber Cancer Institute, and an assistant professor of medicine at Harvard Medical School, all in Boston.

When PFS was stratified by Fotivda cycle 2 exposures quartile, data showed that those who received a higher concentration of Fotivda had the longest median PFS of patients examined. Patients with an exposure ranging from 62 to 177 ng/mL had the longest median PFS at 9.7 months and the median PFS was as follows for those with an exposure ranging from 47.9 to 62.0 ng/mL (median PFS, 9.1 months), 38.4 to 47.9 ng/mL (median PFS, 7.3 months) and 13.9 to 38.4 ng/mL (median PFS, 5.6 months).

“A correlation between [Fotivda exposures] and change in tumor size from baseline was also observed,” McGregor wrote. “Patients in the TiNivo-2 combination therapy arm who received 0.89 mg [of Fotivda] are mostly clustered in the lowest [Fotivda exposure] quartile. As [exposure] quartiles of [Fotivda] increase, patients’ tumor size decreases, indicating [a] higher [Fotivda dose] results in an increased tumor response.”

The Fotivda exposure quartile correlations with changes in tumor size and best overall response (BOR) in the tumor size model revealed the following changes in median BOR for those with an exposure ranging from: 62 to 177 ng/mL (median BOR, –23.8), 47.9 to 62 ng/mL (median BOR, –17.3), 38.4 to 47.9 ng/mL (median BOR, –11.7) and 13.9 to 38.4 ng/mL (median BOR, –7.02). The respective groups included 183, 185, 173 and 176 patients.

In TiNivo-2, the lower dose of Fotivda was given in combination with Opdivo (nivolumab), and modeling data also showed that Opdivo did not affect the pharmacokinetics of Fotivda. Additionally, the incidence of any grade or grade 3 (severe) hypertension was not significantly different between patients who received the two doses of Fotivda.

Data Leading to This Exposure Response Analysis

 was approved by the FDA in March 2021 for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies based on data from TIVO-3. Data from the trial showed that the VEGFR TKI elicited a median overall survival (OS) of 16.4 months in patients (175 patients) versus 19.2 months in patients who received Nexavar (sorafenib, 175 patients). The median PFS was 5.6 months versus 3.9 months, respectively. The recommended dose of Fotivda per the prescribing information and FDA approval is 1.34 mg administered once daily with or without food for 21 consecutive days every 28 days until disease progression or unacceptable toxicity.

Fotivda was given at a lower dose of 0.89 mg for 21 days in a 28-day cycle in TiNivo-2 when it was combined with Opdivo, assuming a risk of hypertension. However, the lower-dose regimen did not improve outcomes when compared with Fotivda monotherapy given at the approved 1.34-mg monotherapy dose. A worsened trend for PFS was observed as patients treated with the doublet (171 patients) experienced a median PFS of 5.7 months versus 7.4 months with the monotherapy (172 patients).

“The results from the TiNivo-2 data set further confirmed that rechallenge with immunotherapy does not add benefit and optimal dosing of [Fotivda] provided the highest clinical benefit following progression on immunotherapy … [exposure response] models show that 1.34 mg [of Fotivda] provides greater antitumor activity than 0.89 mg. The hypertension incidence seems to be comparable, [and] these [exposure response] data suggest that a dose of 1.34 mg [of Fotivda] provides a greater decrease in tumor size and maybe more tolerable,” McGregor wrote in conclusion.

“Integrated efficacy and safety exposure response (ER) analysis of tivozanib (TIVO) for the treatment of renal cell cancer (RCC).” By Dr. Bradley McGregor, et al. 

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Articles

The FDA-approved starting dose of Fotivda (tivozanib) at 1.34 mg demonstrates superior antitumor activity compared to a reduced dose of 0.89 mg in renal cell carcinoma (RCC) patients, with comparable hypertension incidence. Analysis from phase 3 studies shows a strong correlation between higher Fotivda exposure and improved progression-free survival (PFS) and tumor response. The combination of Fotivda with Opdivo did not enhance outcomes, confirming the optimal efficacy of the 1.34 mg dose. These findings suggest that the higher dose offers greater clinical benefits without increased hypertension risk.

Researchers showed that 1.34 mg of Fotivda provided decreased tumor size and may be more tolerable than an 0.89-mg dose among patients with renal cell carcinoma.

FDA-Approved Fotivda Dose More Effective Than Reduced Dose in RCC

Nubeqa plus ADT improved rPFS in mHSPC across all disease volumes, cutting the risk of radiological progression or death by 46%.

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), efficacy outcomes were improved following treatment with Nubeqa (darolutamide) in combination with androgen deprivation therapy (ADT) compared with placebo plus ADT irrespective of disease volume, according to findings from the phase 3 ARANOTE trial.

Data from a subgroup analysis of ARANOTE presented during the 

 demonstrated that patients with high-volume disease who received Nubeqa (315 patients) achieved a median radiological progression-free survival (rPFS) of 30.2 months compared with 19.2 months among those who received placebo (157 patients). Patients with low-volume disease achieved a median rPFS of not reached (NR) in the investigational arm (131 patients) versus NR in the control arm (66 patients).

“The phase 3 ARASENS study demonstrated a greater than 30% reduction in the risk of death with the combination of [Nubeqa] plus ADT and docetaxel, which has become a standard of care for the treatment of patients with mHSPC,” Dr. Fred Saad said during a presentation of the data. “In ARANOTE, [Nubeqa] plus ADT significantly improved rPFS, reducing the risk of radiological progression or death by 46%. Volume of disease is a prognostic factor for patients with mHSPC and here we report a post-hoc analysis of ARANOTE to evaluate the efficacy and safety of [Nubeqa] by disease volume.”

Saad is the director of prostate cancer research at the Montreal Cancer Institute, a uro-oncologist in the Urology Department, and a full professor in the Department of Surgery at the Centre Hospitalier de l'Université de Montréal in Canada.

Radiological progression-free survival (rPFS): the time from treatment initiation to radiographic disease progression or death.

ECOG performance status of 0 to 2: a measure of a patient’s daily functioning, where 0 indicates full activity, and 2 indicates the ability to perform self-care but not work.

Visceral metastases: cancer that has spread to organs such as the liver, lungs or brain.

Gleason Score: a grading system that evaluates the aggressiveness of prostate cancer based on microscopic tumor appearance.

Overall survival (OS): the time from diagnosis or treatment start to death from any cause.

Time to initiation of subsequent anticancer therapy: the duration from treatment start to the beginning of the next line of cancer treatment.

Time to metastatic castration-resistant prostate cancer (mCRPC): the time from initial treatment to the development of resistance to hormone therapy with metastases.

Time to prostate-specific antigen (PSA) progression: the duration until a confirmed rise in PSA levels, indicating potential disease progression.

Rates of undetectable PSA: the proportion of patients achieving PSA levels below the detection threshold.

Time to pain progression: the time until a clinically significant worsening of pain related to cancer.

In November 2024, the FDA accepted a supplemental new drug application (sNDA) seeking the approval of Nubeqa plus ADT for the treatment of patients with mHSPC. The sNDA was supported by previous data from ARANOTE. Findings from ARANOTE presented during the 2024 ESMO Congress showed that regardless of disease volume patients who received Nubeqa plus ADT (446 patients) achieved a median rPFS of NR versus 25 months in the placebo arm (223 patients).

Diving Into the ARANOTE Trial and Baseline Characteristics

ARANOTE was a global, double-blind study that enrolled patients with mHSPC who had an ECOG performance status of 0 to 2. Patients were stratified based on the presence of visceral metastases (yes versus no) and receipt of prior local therapy (yes versus no). Eligible patients were randomly assigned 2:1 to receive Nubeqa at a dose of 600 milligrams twice daily or placebo, both in combination with ADT.

The primary end point was rPFS by central blinded review. Secondary end points included overall survival (OS), time to initiation of subsequent anticancer therapy, time to metastatic castration-resistant prostate cancer (mCRPC), time to prostate-specific antigen (PSA) progression, rates of undetectable PSA (less than 0.2 ng/mL), time to pain progression and safety.

In the post-hoc analysis that Saad presented, patients were evaluated based on disease volume per CHAARTED criteria. High-volume disease was defined as the presence of visceral metastases and/or at least four bone lesions with at least one lesion beyond the vertebral bodies and pelvis. Low-volume disease was defined as not meeting the high-volume criteria.

At baseline, the median age of the overall patient population was 70 years. Most patients had a Gleason score of at least 8 at initial diagnosis (68.3%) and de novo metastasis at initial diagnosis (72.5%). The study also included patients with visceral metastases (12%), those who had received prior local therapy (17.9%), and those with an ECOG performance status of 0 (49.8%). The median serum PSA level at baseline was 21.3 ng/mL.

Further Efficacy and Safety Data from the Analysis

Additional findings from the post-hoc analysis showed that patients in the high- and low-volume groups experienced a delayed time to mCRPC with Nubeqa plus ADT versus placebo plus ADT, which was consistent with the benefit observed in the overall population. Patients with high-volume disease in the investigational and control arms achieved a median time to mCRPC of NR versus 12.4 months, respectively. In the low-volume group, the median time to mCRPC was NR versus 19.8 months, respectively.

The addition of Nubeqa to ADT also led to a benefit compared with placebo plus ADT across all secondary end points examined. The greatest benefits were reported in time to initiation of subsequent systemic anticancer therapy in patients with low-volume disease, time to PSA progression in patients with low-volume disease and time to PSA progression in patients with high-volume disease.

“OS results were immature, but suggestive of a benefit with [Nubeqa] versus placebo,” Saad noted.

Evaluable patients with high-volume disease in the Nubeqa arm (304 patients) had undetectable PSA levels 24, 36 and 48 weeks after random assignment at rates of 44%, 48% and 50%, respectively; 55% of these patients achieved undetectable PSA at any time. Comparatively, patients in the placebo arm (148 patients) achieved undetectable PSA at rates of 11%, 13%, 14% and 16%, at the respective time points.

Patients with low-volume disease who received Nubeqa (121 patients) also experienced undetectable PSA levels at higher rates compared with those who received placebo (63 patients) at the 24- (72% versus 17%, respectively), 36- (78% versus 19%) and 48-week (79% versus 19%) time points. Patients experienced undetectable PSA at any time at rates of 83% versus 25%, respectively.

In terms of safety, patients with high-volume disease who received Nubeqa (314 patients) or placebo (156 patients) both experienced any-grade treatment-emergent side effects (TEAEs; 93% versus 91.7%, respectively), grade 3 (severe) or 4 (life-threatening) TEAEs (31.2% versus 31.2%), serious TEAEs (28.3% versus 25.6%) and TEAEs leading to study drug discontinuation (7.3% versus 8.3%). Patients with low-volume disease in the Nubeqa (131 patients) and placebo (65 patients) arms also experienced any-grade TEAEs (86.3% versus 86.2%), grade 3 or 4 TEAEs (29.8% versus 26.2%), serious TEAEs (12.2% versus 18.5%) and TEAEs leading to study drug discontinuation (3.1% versus 10.8%).

“Efficacy outcomes with [Nubeqa] plus ADT were improved versus placebo plus ADT regardless of disease volume,” Saad said in conclusion. “[Nubeqa] plus ADT was well tolerated in both high-volume and low-volume subgroups with low treatment discontinuation rates consistent with the overall population and reconfirming the established tolerability of darolutamide. Patients with low-volume mHSPC had marked treatment efficacy with minimal treatment burden.”

“Darolutamide plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC) by disease volume: subgroup analysis of the phase 3 ARANOTE trial.” By Dr. Fred Saad, et al. 

“Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial.” By Dr. Fred Saad, et al. 

Nubeqa (darolutamide) combined with androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to placebo plus ADT, regardless of disease volume. The ARANOTE trial demonstrated a 46% reduction in the risk of radiological progression or death. High-volume disease patients achieved a median rPFS of 30.2 months, while low-volume disease patients' rPFS was not reached. Nubeqa plus ADT was well tolerated, with low treatment discontinuation rates, confirming its established safety profile.

Nubeqa plus ADT improved rPFS in mHSPC regardless of disease volume, reducing the risk of radiological progression or death by 46%, per ARANOTE data.

Nubeqa Plus ADT Effective in mHSPC Regardless of Disease Volume

Cabometyx improved progression-free survival in patients with advanced neuroendocrine tumors originating in the gastrointestinal tract compared to placebo.

Compared with placebo, Cabometyx (cabozantinib) improved progression-free survival (PFS) after progression on prior therapy for extrapancreatic neuroendocrine tumors (NETs) with a primary tumor arising in the gastrointestinal (GI) tract, as demonstrated in subgroup data from the CABINET trial presented at the 

The VEGF-targeted agent also improved PFS versus placebo in patients with various clinical factors, except in those with a primary site of a non-midgut GI tumor.

Findings from the analysis revealed that patients in the extrapancreatic NET cohort with a primary tumor arising in the GI tract (116 patients) experienced a median PFS of 8.5 months in the Cabometyx arm (70 patients) versus 5.6 months in the placebo arm (46 patients). Best overall responses in the Cabometyx and placebo arms included confirmed partial response (1% versus 0%), stable disease (69% versus 65%) and progressive disease (9% versus 26%), and patients were also not evaluable (21% versus 9%), respectively.

“New therapeutic options are needed for patients with advanced NETs,” Dr. Jonathan Strosberg, leader of the Neuroendocrine Tumor Division and Department of Gastrointestinal Oncology Research Program at Moffitt Cancer Center in Tampa, Florida, wrote in a poster presentation of the findings. “Potential benefit was observed across clinical factors including grade, functional status, [use] concurrent somatostatin analogs and prior treatment.”

 showed that Cabometyx significantly improved PFS versus placebo in patients with previously treated, progressive advanced extrapancreatic or pancreatic NETs. Confirmed objective response rates were 5% and 19% in patients with extrapancreatic and pancreatic NETs, respectively.

Progression-free survival: the time during and after treatment when a patient with cancer is alive without the disease worsening.

Best overall response: the best result seen during the treatment period in terms of how the cancer responded to the treatment.

Objective response rate: the percentage of patients with a complete or partial response to treatment within a period of time.

ECOG performance score of 1 or 2: the patient is able to walk and do light activities but cannot do strenuous activities, or they are able to take care of themselves but unable to work.

Patients enrolled in CABINET had grade I to III well to moderately differentiated NETs and had experienced disease progression within 12 months prior to random assignment following treatment with at least one prior FDA-approved systemic therapy, not including somatostatin analogs. They were then assigned to the extrapancreatic NET arm or pancreatic NET arm and randomly assigned to receive Cabometyx or placebo. The main focus of the trial was to assess PFS.

Baseline Patient Characteristics From the Subgroup Analysis

The median number of prior systemic therapies received, not including somatostatin analogs, was one in both the Cabometyx and placebo arms. All patients had received somatostatin analogs previously, and most had received Afinitor (everolimus; 61% versus 54%) or Lutathera (lutetium Lu 177 dotatate; 79% versus 74%), and some were given Temodar (temozolomide)–based therapies (17% versus 15%).

The median duration of therapy was 5.8 months among patients treated with Cabometyx (68 patients) and 3.7 months among those given placebo (45 patients). Additionally, 13 versus 7 patients remained on treatment in the respective arms. Reasons for discontinuation included progressive disease, side effects, withdrawn consent and death on study.

Cabometyx yielded a PFS benefit versus placebo among all clinical factor groups examined in this subgroup analysis aside from in those with a primary tumor site of non-midgut GI. The most pronounced benefit was seen in those who had not received prior Lutathera, had grade I disease, had an ECOG performance score of 1 or 2 and who had a primary tumor site of midgut GI.

The safety profile of Cabometyx was consistent with previously reported data, and in this patient population treated with the agent (68 patients) versus placebo (45 patients), grade 3 (severe) to 4 (life-threatening) side effects occurred in 60% versus 18% of patients. Notable grade 3 to 4 side effects included hypertension (19% versus 4%), diarrhea (13% versus 4%) and fatigue (10% versus 4%), respectively. Grade 5 (death) toxicities that may have been related to study treatment occurred in three patients treated with Cabometyx; one patient experienced cardiac arrest, and the other two causes of death were not specified.

“Efficacy and safety of cabozantinib for advanced gastrointestinal (GI) neuroendocrine tumors (NET) after progression on prior therapy: subgroup analysis of the phase 3 CABINET trial (Alliance A021602).” By Dr. Jonathan Strosberg, et al. Presented at: 2025 Gastrointestinal Cancers Symposium; 2025 Jan 16-18; San Francisco, CA. Abstract 666

Cabometyx (cabozantinib) demonstrated improved progression-free survival (PFS) in patients with extrapancreatic neuroendocrine tumors (NETs) originating in the gastrointestinal (GI) tract, as shown in the CABINET trial. The trial revealed a median PFS of 8.5 months for Cabometyx versus 5.6 months for placebo. The drug showed benefits across various clinical factors, except for non-midgut GI tumors. Safety data indicated a higher incidence of severe side effects with Cabometyx. The trial focused on patients with progressive NETs post prior systemic therapy, excluding somatostatin analogs.

A study showed Cabometyx improved time before disease progression in advanced digestive NETs compared with placebo.

Cabometyx Shows Promise for Treating Advanced NETs Originating in the GI Tract

Scemblix outperformed standard tyrosine kinase inhibitors in treating chronic myeloid leukemia, with higher response rates and fewer side effects, according to data from the phase 3 ASC4FIRST trial.

Scemblix (asciminib) further solidified its role in treating chronic myeloid leukemia (CML) as 96-week data showed it outperformed standard-of-care investigator-selected tyrosine kinase inhibitors (TKIs) and met key secondary goals of the phase 3 ASC4FIRST trial.

Data presented at the 2024 ASH Annual Meeting showed that the major molecular response (MMR) rate at week 96 continued to be superior among patients who received Scemblix (201 patients) versus all IS-TKIs (204 patients), meeting a key secondary end point of the trial; rates were 74.1% versus 52%, respectively with investigators noting the difference was 22.4%. This represented an increase in MMR as the 48-week MMR rates were 67.7% and 49%, respectively, which originally met the primary end point of the trial.

“The 96-week data that I am showing you today for the first time [reveal that] all of these comparisons against all TKIs, [Gleevec] and second generation TKIs, favor [Scemblix]. The ones that are powered [for it] are statistically significant [as well],” Dr. Jorge E. Cortes said in a presentation of the data. Cortes is director for the Georgia Cancer Center and the Cecil F. Whitaker Jr, GRA Eminent Scholar Chair in Cancer in Augusta.

The 96-week MMR rates were also consistently higher with Scemblix across the trial strata. In the Gleevec (imatinib) stratum, patients who received Scemblix (101 patients) experienced a 96-week MMR rate of 76.2% versus 47.1% among those in the IS-TKI group (102 patients), for a difference of 29.7%. In the second-generation TKI stratum, the 96-week MMR rates were 72% in the Scemblix group (100 patients) and 56.9% in the IS-TKI group (102 patients) for a difference of 15.1%.

Major molecular responses (MMR): MR4 and MR4.5, measure the reduction of cancer cells in the blood, with lower values indicating deeper responses and better long-term outcomes for CML patients.

Tyrosine kinase inhibitors (TKIs): a type of targeted therapy that blocks specific proteins involved in cancer cell growth.

Arterial occlusive events: blockage of blood flow in an artery.

EUTOS long-term survival score (ELTS): a scoring system used to predict the long-term survival of patients with chronic myeloid leukemia.

The FDA Approval of Scemblix and ASC4FIRST Trial Enrollment

The Oct. 29, 2024 FDA accelerated approval of Scemblix for the treatment of adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CP) was based on the 48-week MMR data from ASC4FIRST. Findings supporting the approval showed that the 48-week MMR rate was 68% in the Scemblix group versus 49% in the IS-TKIs group, for a difference of 19%, meeting one of the trial’s primary end points. The other primary end point, 48-week MMR rate with Scemblix versus IS-TKIs in the Gleevec stratum, was also met in the primary analysis of ASC4FIRST with high statistical significance. The MMR rate was 69% versus 40%, respectively, for a difference of 30%.

ASC4FIRST enrolled adults newly diagnosed Philadelphia chromosome-positive CML-CP who had not been previously treated with a TKI. Patients received Scemblix at 80 milligrams once daily or IS-TKIs at label doses. Physicians and patients consulted to select a TKI should the patient be randomly assigned to the IS-TKI group of the trial and stratification occurred by prerandomization TKI selection and EUTOS long-term survival score (ELTS) risk category. Secondary end points of the trial included 96-week MMR with Scemblix versus all IS-TKIs and 96-week MMR with Scemblix versus IS-TKIs in the Gleevec stratum.

“The patient characteristics were very well balanced,” Cortes said. “When you look at the individual strata, however, it becomes obvious that the patients in the Gleevec strata were somewhat older and had a higher Framingham [risk] score, whereas the patients in the second-generation TKI strata tended to have more patients in the high-risk ELTS risk classification.”

Scemblix’s Safety Profile Continues to Best Gleevec and Second-Generation TKIs

By the 96-week data cutoff, safety and tolerability data continued to be more favorable with Scemblix compared with Gleevec and second-generation TKIs. The risk of treatment discontinuation due to side effects was 54% lower with Scemblix versus second-generation TKIs.

“[Scemblix’s] safety and tolerability profile continued to be better than that of Gleevec and second-generation TKIs after longer follow-up and [data were] consistent with its known safety profile,” Cortes said.

In the safety populations of patients who received Scemblix (200 patients), Gleevec (99 patients), and second-generation TKIs (102 patients), grade 3 (severe) or worse side effects (44.5% versus 49.5% versus 59.8%, respectively), side effects leading to treatment discontinuation (5% versus 13.1% versus 12.7%) and side effects leading to dose adjustment/interruption (33% versus 41.4% versus 57.8%) occurred.

Additionally, arterial occlusive events (AOEs) did not occur frequently with any agents in the trial. Four patients experienced at least one AOE in the Scemblix group (200 patients), and three patients experienced at least one event in the second-generation TKI group (102 patients); one patient in each of the aforementioned groups experienced a grade 3 or worse event and no patients in the Gleevec group (99 patients) experienced an AOE.

“[Scemblix’s] favorable risk-benefit profile compared with all IS-TKIs, Gleevec, and second-generation TKIs in patients with newly diagnosed CML-CP reinforces the use of Scemblix as a SOC for this patient population,” Cortes concluded.

At the Oct. 22, 2024, data cutoff, more patients were ongoing treatment with Scemblix (81.6%) than all IS-TKIs (60.3%). Patients in the Scemblix group versus all IS-TKIs group discontinued treatment (17.9% versus 38.2%, respectively) due to unsatisfactory therapeutic effect (9.5% versus 20.6%), adverse effect (AE; 6% versus 12.7%), progressive disease (1% versus 2%), physician decision (0.5% versus 0%), protocol deviation (0.5% versus 1%), patient decision (0.5% versus 1.5%), or pregnancy (0% versus 0.5%).

“The discontinuation rate was twice as high with all IS-TKIs compared with [Scemblix],” Cortes noted.

Furthermore, the cumulative incidence of MMR was higher with Scemblix (80.5%) versus all IS-TKIs (62.1%) at 96-weeks. Across strata, this was also true; in the Gleevec stratum rates were 80% in the Scemblix group and 56.5% in the IS-TKI group, and in the second-generation TKI stratum rates were 81% in the Scemblix group and 67.6% in the IS-TKI group.

At week 96, data on deep molecular responses revealed that 48.8% of patients who received Scemblix achieved an MR4 and 30.9% achieved an MR4.5; these respective rates were 27.5% and 17.7% in the all IS-TKIs group. In the Gleevec stratum 52.5% of patients treated with Scemblix experienced an MR4 and 35.6% experienced an MR4.5; respective rates were 23.5% and 11.8% in the IS-TKI group. Additionally, in the second-generation TKI stratum, 45% of patients treated with Scemblix experienced an MR4 and 26% experienced an MR4.5; respective rates were 31.4% and 23.5% in the IS-TKI group.

“There is a continued and increasing difference in favor of [Scemblix] [versus IS-TKI] for both MR4 and MR4.5,” Cortes explained. “One important analysis is to look at the difference in subsets of patients. These are small subsets [and the study was] not powered for any one of them, but it is very good to see that in any individual subgroup — whether it’s by ELTS, sex, race and ethnicity, age category [or] Framingham score — all of them favor the treatment of [Scemblix] in terms of the rate of MMR at [week] 96. There’s really no subset of patients where we don’t see at least a trend in benefit for [Scemblix] compared with the investigator selected control [group].”

Investigators also examined postbaseline treatment-emergent BCR::ABL1 gene mutations by next-generation sequencing. “In summary, all the mutations that emerged in this study with the treatment [of] [Scemblix] have been myristoyl pocket mutations,” Cortes noted.

“Scemblix (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the pivotal phase 3 ASC4FIRST study” by Dr. Jorge E. Cortes et al., 

Scemblix (asciminib) has demonstrated superior efficacy and safety in treating chronic myeloid leukemia (CML) compared to standard tyrosine kinase inhibitors (TKIs) in the phase 3 ASC4FIRST trial. At 96 weeks, Scemblix showed a higher major molecular response (MMR) rate than all investigator-selected TKIs, including Gleevec and second-generation TKIs. The FDA granted accelerated approval based on earlier 48-week data. Scemblix also exhibited a favorable safety profile, with lower rates of severe side effects and treatment discontinuation. The trial highlighted Scemblix's potential as a standard of care for newly diagnosed CML patients.

Scemblix resulted in better outcomes and fewer side effects compared to standard tyrosine kinase inhibitor therapies in patients with chronic myeloid leukemia.

Megan Hollasch

FDA-Approved Fotivda Dose More Effective Than Reduced Dose in RCC

Nubeqa Plus ADT Effective in mHSPC Regardless of Disease Volume

Cabometyx Shows Promise for Treating Advanced NETs Originating in the GI Tract

Scemblix May Outperform Standard Treatments for Chronic Myeloid Leukemia

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