A real-world retrospective cohort study showed that the median overall survival (OS) with frontline FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) was numerically lower than the median OS that was previously shown with frontline NALIRIFOX (liposomal irinotecan, 5-fluorouracil [5-FU], leucovorin, and oxaliplatin) in this population in the phase 3 NAPOLI 3 trial (NCT04083235).

The real-world findings, which were presented at the 

2025 ASCO Gastrointestinal Cancers Symposium

, demonstrated that treatment with FOLFIRINOX in a trial-aligned cohort of patients who met the eligibility criteria for the NAPOLI 3 trial (n = 219) elicited a median OS of 9.1 months (95% CI, 7.8-10.9) compared with 11.1 months (95% CI, 10.0-12.1) with NALIRIFOX in NAPOLI 3. Furthermore, the median OS was 9.0 months (95% CI, 8.5-9.3) for all-comer patients with mPDAC treated with first-line FOLFIRINOX between January 1, 2014, and February 29, 2024 (n = 3271). An additional trial-aligned cohort of patients treated with modified FOLFIRINOX (mFOLFIRINOX; n = 154) experienced a median OS of 8.6 months (95% CI, 7.3-10.5).

“[The] NALIRIFOX regimen in the NAPOLI 3 trial showed numerically improved OS compared to [FOLFIRINOX], including [mFOLFIRINOX], in the real-world setting,” Paul Cockrum, PharmD, director of American Oncology HEOR at Ipsen Pharma, wrote with coauthors in the study.

 “Analyses adjusting for baseline characteristics are warranted and will provide further insights for the comparative efficacy of the 2 regimens.”

The real-world analysis used de-identified, patient-level, longitudinal data from the Flatiron Electronic Health Record collected between January 1, 2014, and February 29, 2024, to construct the 3 cohorts for the study. All adult patients identified with confirmed diagnoses of mPDAC on or after January 1, 2014, who were treated with first-line FOLFIRINOX encompassed the all-comer cohort of the analysis. A second, trial-aligned cohort included members of the all-comer cohort who met the NAPOLI 3 trial eligibility criteria.

A third cohort included a subgroup of patients in the second cohort who were treated with mFOLFIRINOX. mFOLFIRINOX in the third cohort was defined as an initial dose of 150 mg/m

 or lower of irinotecan or an initial cumulative dose of 2720 mg/m

 or lower of 5-FU during the first cycle. 

The median age on the index date of the trial-aligned cohort was 65.0 years (interquartile range [IQR], 59.0-71.0) compared with 64.0 years (IQR, 58.0-70.0) across all-comers and 65.5 years (IQR, 60.0-72.0) in the mFOLFIRINOX cohort. Furthermore, male patients accounted for 54.3%, 57.9%, and 55.8% of each cohort; 66.7%, 64.8%, and 64.9% of patients in these respective cohorts were White; and the respective median times from metastatic diagnosis to index date were 3.0 weeks (IQR, 2.0-4.6), 3.0 weeks (IQR, 1.9-4.7), and 3.0 weeks (IQR, 2.0-4.4).

All patients in the trial-aligned and mFOLFIRNOX cohorts, as well as 82.9% of those in the all-comer cohort, had a known ECOG performance status. Additionally, 53.0% of patients in the trial-aligned cohort, 34.7% of all-comers, and 50.0% of those in the mFOLFIRNOX cohort had an ECOG performance status of 0. Data showed that 7.8%, 11.3%, and 9.7% of patients in these respective cohorts were previously treated with surgery, and 10.5%, 13.8%, and 12.3% of these patients, respectively, were treated with prior chemotherapy.

The phase 3 NAPOLI 3 trial enrolled treatment-naive patients with mPDAC to receive either NALIRIFOX or nab-paclitaxel (Abraxane) plus gemcitabine.

 Patients in the NALIRIFOX arm received 50 mg/m

 of fluorouracil sequentially as a continuous intravenous infusion over 46 hours on days 1 and 15 of a 28-day cycle. Those in the standard-of-care cohort received 125 mg/m

of gemcitabine intravenously on days 1, 8, and 15 of a 28-day cycle.

In the NALIRIFOX arm, the median patient age was 64.0 years (range, 20-85), most patients were male (53%), and most patients were White (82%). Most patients on trial had an ECOG performance status of 1 (58%), 3 or more metastatic sites (39%), liver metastases (80%), and a baseline CA 19-9 level of 37 U/mL or higher (84%). Additionally, 6% of patients had undergone any previous anticancer therapy, including a surgical procedure (5%), chemotherapy (4%), and radiotherapy (3%). 

Cockrum P, Chang R, Yu L, et al. Overall survival (OS) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line (1L) FOLFIRINOX (FFX): bridging the gap between the NAPOLI 3 trial and real-world practice. 

2025;43(suppl 4):690. doi:10.1200/JCO.2025.43.4_suppl.690

Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. 

 2023;402(10409):1272-1281. doi:10.1016/S0140-6736(23)01366-1

Articles

A retrospective cohort study compared the median overall survival (OS) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with frontline FOLFIRINOX versus NALIRIFOX. The study found that NALIRIFOX demonstrated a numerically higher median OS than FOLFIRINOX in both trial-aligned and real-world settings. The analysis utilized de-identified patient data from the Flatiron Electronic Health Record, focusing on patients treated between 2014 and 2024. The study suggests further analyses adjusting for baseline characteristics to better understand the comparative efficacy of these regimens.

The median OS with frontline FOLFIRINOX was numerically lower than that seen with frontline NALIRIFOX in patients with metastatic PDAC.

First-Line FOLFIRINOX Fails to Improve OS vs First-Line NALIRIFOX in Metastatic PDAC

The addition of evorpacept (ALX148) to trastuzumab (Herceptin), paclitaxel, and ramucirumab (Cyramza; TRP) yielded more durable responses and favorable survival outcomes compared with TRP alone in patients with HER2-positive gastric or gastroesophageal junction (GEJ) cancer, particularly among those with confirmed HER2-positive disease by circulating tumor DNA (ctDNA) or fresh biopsy, according to results from the phase 2/3 ASPEN-06 trial (NCT05002127) presented at the 

Efficacy findings from the trial revealed that the confirmed objective response rate (ORR) was 41.3% (95% CI, 29.0%-54.4%) in the evorpacept combination arm vs 26.6% (95% CI, 16.3%-39.1%) with TRP alone. In the respective arms, 1.6% and 1.6% of patients achieved a complete response, and 39.7% and 25.0% achieved a partial response. Additionally, the median duration of response (DOR) was 15.7 months (95% CI, 7.7-not reached [NR]) with evorpacept plus TRP and 9.1 months (95% CI, 5.3-NR) with TRP alone.

The median progression-free survival (PFS) was 7.5 months (95% CI, 5.5-12.9) with the investigational regimen and 7.4 months (95% CI, 4.6-9.0) with TRP alone (HR, 0.77; 95% CI, 0.49-1.20). Additionally, HER2–positive expression confirmed via fresh biopsy conferred bolstered antitumor benefit, with an ORR of 59.1% (95% CI, 36.4%-79.3%) in the evorpacept arm vs 23.1% (95% CI, 9.0%-43.6%) in the TRP arm and a median DOR of 15.7 months (95%, 4.0-NR) vs 14.5 months (95% CI, 7.4-NR), respectively.

“[Evorpacept plus] TRP showed promising activity for patients with HER2–positive gastric and GEJ cancer with a response rate above 41.3% compared with 26.6% with TRP alone,” Kohei Shitara, MD, director of the Department of Gastrointestinal Oncology at National Cancer Center Hospital East in Kashiwa, Japan, said in the oral presentation.

 “The benefit of [evorpacept] was especially [observed] in patients with confirmed HER2–positive [expression] in fresh biopsy or ctDNA, in that its mode of action was able to enhance the activity of trastuzumab. This efficacy, as well as acceptable safety profile, support the further development of [evorpacept plus] TRP in patients with gastric and GEJ cancers.”

The intent-to-treat (ITT) population included patients with HER2–positive gastric or GEJ cancer who progressed on 2 or 3 previous lines of HER2-directed therapy (n = 127). Patients were randomly assigned 1:1 to receive either evorpacept in combination with TRP (n = 63) or TRP without evorpacept (n = 64).

Dosing in the evorpacept arm consisted of 30 mg/kg of intravenous evorpacept twice weekly, 6 mg/kg then 4 mg/kg of trastuzumab twice weekly, 8 mg/kg of ramucirumab twice weekly, and 80 mg/m

 of paclitaxel on days 1, 8, and 15 of a 28-day cycle. Dosing in the TRP only arm consisted of the same dosing without evorpacept.

The median ages of patients in the investigational and control arms were 64 years (range, 34-81) and 63 years (range, 31-86), respectively. Patients were primarily Asian (49.2% vs 48.4%), or White (30.2% vs 29.7%), and most patients had an ECOG performance status of 1 (52.4% vs 57.8%). Furthermore, the most common type of cancer in either arm was gastric (76.2% vs 68.8%), most patients received second-line therapy (77.8% vs 68.8%), and most patients had a HER2 status of IHC 3+ (82.5% vs 82.8%).

The phase 2 primary efficacy end point was ORR over an assumed historical control of 30% and over internal control.

 Secondary end points included DOR, PFS, and overall survival.

Among patients with HER2-positive disease confirmed via fresh biopsy or ctDNA positivity, the confirmed ORR was 48.9% (95% CI, 34.1%-63.9%) in the evorpacept arm vs 24.5% (95% CI, 13.3%-38.9%) in the TRP only arm. Additionally, the median DOR in this subgroup was 15.7 months (95% CI, 7.7-NR) vs 9.1 months (95% CI, 3.5-NR), respectively.

Among those with a HER2-positive fresh biopsy (n = 48), the median PFS was 9.5 months (95% CI, 5.4-19.5) with evorpacept plus TRP vs 7.1 months (95% CI, 2.9-9.1) with TRP alone (HR, 0.62; 95% CI, 0.28-1.36). Of those with a HER2-positive biopsy or ctDNA positivity (n = 96), the median PFS was 7.5 months (95% CI, 5.5-14.7) and 6.7 months (95% CI, 4.0-9.0) in each respective arm (HR, 0.64; 95% CI, 0.39-1.07).

The most common grade 3 treatment-emergent adverse events (TEAEs) in the investigational and control arms included decreased neutrophil counts (both 19.0%), anemia (22.2% vs 17.5%), neutropenia (17.5% vs 11.1%), and hypertension (9.5% vs 6.3%). There were 11 grade 5 TEAEs, 2 of which were related to treatment and included individual occurrences of esophageal perforation and pneumopathy.

Shitara K, Wainberg Z, Tabernero J, et al. Final analysis of the randomized phase 2 part of the ASPEN-06 study: A phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2–overexpressing gastric/gastroesophageal cancer (GC). 

 2025;43(suppl 4):332. doi:10.1200/JCO.2025.43.4_suppl.332

A study of evorpacept (ALX148) in patients with advanced HER2+ gastric cancer (ASPEN-06). ClinicalTrials.gov Updated September 19, 2024. Accessed January 23, 2025. https://tinyurl.com/yzf33xdk

Evorpacept, when added to trastuzumab, paclitaxel, and ramucirumab, demonstrated improved response rates and survival outcomes in HER2-positive gastric or gastroesophageal junction cancer compared to the standard regimen. The ASPEN-06 trial showed a higher objective response rate and longer duration of response with the evorpacept combination, particularly in patients with confirmed HER2-positive status via ctDNA or fresh biopsy. The investigational regimen also exhibited a favorable safety profile, supporting its further development. The trial included patients who had progressed on previous HER2-directed therapies, with dosing regimens specified for both study arms.

Evorpacept plus TRP produced superior ORR, DOR, and PFS outcomes vs TRP alone in patients with HER2-positive gastric or gastroesophageal junction cancer.

Evorpacept Plus TRP Generates Superior Antitumor Responses, Survival Outcomes in HER2+ Gastric/GEJ Cancer  

An ancillary analysis of the phase 3 NRG/RTOG 9804 (NCT00003857) and ECOG-ACRIN E5194 (NCT00002934) trials showed that tamoxifen (Soltamox) was associated with a reduced risk of 15-year ipsilateral breast recurrence (IBR) in patients with good-risk ductal carcinoma in situ (DCIS) treated without radiation therapy (RT). Data were presented at the 

2024 San Antonio Breast Cancer Symposium (SABCS)

Findings showed that treatment with tamoxifen elicited a statistically significant reduction in 15-year overall IBR by 11.4% (95% CI, 7.9%-15.5%) with tamoxifen vs 19.0% (95% CI, 15.3%-22.9%) without it (HR, 0.52; 95% CI, 0.35-0.77; 

 = .001). The 15-year risk of DCIS IBR was not significantly impacted by tamoxifen (5.5%) compared with those who did not receive it (8.1%; HR, 0.61; 95% CI, 0.34-1.08). For those with invasive IBR, there was a significant reduction with tamoxifen use (6.0%) compared with those who did not (11.5%; HR, 0.47; 95% CI, 0.27-0.80; 

 = .005). A non-significant reduction was also observed with contralateral breast events (CBE; 8.1%; HR, 0.61; 0.34-1.08; 

“Tamoxifen reduced the HR––or trended toward reducing the HR––across all subsets of patients, suggesting a broad benefit in the patients included in this analysis,” Jean Wright, MD, professor and chair of Radiation Oncology at the University of North Carolina, said in an oral presentation at SABCS. “We now have more thorough data to present to patients who are considering radiation therapy with respect to their endocrine therapy decision... Our data shows that it is important to evaluate the impact of endocrine therapy [for patients] who do not receive radiation therapy.”

Patients in the ancillary analysis of the NRG/RTOG and ECOG-ACRIN E5194 trials were included if they were considered to have “good risk” DCIS after breast-conserving surgery (BCS). “Good risk” was defined as a DCIS size of 2.5 cm or smaller, grade 1 or 2, and a margin greater than or equal to 3 mm. The use of tamoxifen was tracked in both trials, with both assessing tamoxifen alone on IBR in patients defined as “good risk” not receiving radiation therapy.

In the combined treatment analysis, 878 patients with “good risk” DCIS were included, 378 (43%) of whom received tamoxifen. Across both trials, the median age was 59 years (range, 28-88), with 80% of patients 50 years or older. Furthermore, 89% of patients were White.

Most patients had a DCIS margin width between 3 and 9 mm (n = 534, 61%) whereas only 19% had a margin width of 10 mm or greater (n = 169, 19%; 

 .0001). Additionally, 48% (n = 421) of patients had a pathologic size of 5 mm or smaller vs 35% (n = 310) between 6 and 10 mm, and 17% (n = 145) had a pathologic size greater than 10 mm (

Furthermore, most patients had DCIS nuclear grade 2 (n = 496, 56%), with a subset of patients initially classified as low or intermediate grade upgraded to grade 3 (n = 110, 13%) after subsequent pathology review was conducted in the ECOG-ACRIN E5194 study (

Subgroup analysis revealed a notably high benefit in patients with a margin width of 10 mm or greater, at an IBR of 5.4% (95% CI, 1.3%-14.1%) with tamoxifen vs 24.3% (95% CI, 15.0%-34.8%) without. Furthermore, patients with a pathologic size greater than 10 mm saw a notable benefit with tamoxifen, with an IBR of 14.4% (95% CI, 5.0%-28.4%) with the agent vs 29.7% (95% CI, 19.8%-40.2%) without it.

Wright JL. Impact of tamoxifen only after breast conservation surgery for “good risk” duct carcinoma in situ: results from the NRG oncology/RTOG 9804 and ECOG-ACRIN E5194 trials. Presented at: San Antonio Breast Cancer Symposium 2024; December 10-13, 2024; San Antonio, TX. Abstract GS2-02

Tamoxifen significantly reduces the risk of 15-year ipsilateral breast recurrence (IBR) in patients with good-risk ductal carcinoma in situ (DCIS) who do not receive radiation therapy. The analysis of phase 3 NRG/RTOG 9804 and ECOG-ACRIN E5194 trials demonstrated a reduction in overall IBR and invasive IBR with tamoxifen use. Subgroup analysis highlighted greater benefits in patients with larger margin widths and pathologic sizes. These findings provide valuable data for patients considering endocrine therapy without radiation, emphasizing the importance of evaluating tamoxifen's impact in this context.

Tamoxifen reduced the risk of invasive ipsilateral breast recurrence in patients with good-risk ductal carcinoma in situ.

Tamoxifen Reduces Ipsilateral Breast Recurrence in Good-Risk Ductal CIS

CAR T Cells in R/R Non-Hodgkin Lymphoma | 

Image Credit: © Tatiana Shepleva - stock.adobe.com

Transposon-engineered BAFF ligand–based CAR T cells (LMY-920) induced responses with a tolerable safety profile among 3 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL), according to data from a phase 1 trial (NCT05312801) presented at the 

Data from the trial reveal that a single grade 1 cytokine release syndrome (CRS) event was reported among the 3 patients, with no immune effector-cell associated neurotoxicity syndrome (ICANS) incidence reported. Additionally, a complete response was observed in one patient with transformed follicular lymphoma. A mixed response, characterized by a decrease in FDG uptake and a decrease in size of all lesions, and stable disease were recorded among 2 other patients with mantle cell lymphoma (MCL). Furthermore, one grade 2 incident of COVID-19 infection was observed in a 55-year-old patient with MCL.

“In terms of safety, it was quite good. [There were] low rates of low-grade CRS among 3 patients, no ICANS was observed, the standard hematologic toxicity [one would] expect from the lymphodepleting regimen [was observed], and [there was] little other relevant toxicity,” Matthew Spear, MD, chief medical officer at Denovo Biopharma, said in a presentation of the study findings. “The efficacy was quite remarkable. [The first] patient [had] diffuse large B-cell lymphoma [and achieved] a complete response with resolution of all FDG avidity on PET scan.”

Investigators of the phase 1 study enrolled 3 patients with histologically confirmed B-cell NHL who had relapsed after 2 or more lines of therapy, were refractory to prior chemotherapy, or had progressive disease at 12 or fewer months following autologous stem cell transplantation (ASCT). All patients were assigned to receive 1 x 106 BAFF CAR T-cells/kg in a 3+3 dose escalation. Prior to treatment, patients underwent lymphodepletion with fludarabine at 30 mg/m2 and cyclophosphamide at 500 mg/m2 once daily for 3 days.

Among the patients enrolled, ages varied from 55 to 81 years, and they received 2 to 4 prior lines of therapy. The 2 patients with MCL had 

 mutations, one of whom had prior Bruton tyrosine kinase inhibitor therapy and ASCT.

The primary end point of the study was assessing the recommended phase 2 dose of LMY-920. Key secondary end points included toxicity, disease response, duration of response, progression-free survival, overall survival, and incidence of anti-LMY-920 antibodies.

“Overall, [this study is] somewhat interesting in that this is the first of its kind CAR T-cell therapy testing patients using a BAFF-ligand to target NHL. It is also a transposon engineer target system, which are still relatively uncommon in the CAR T-cell field,” Spear said in the presentation. “Safety and efficacy at this point are looking good. This could be extrapolated farther, and that is perhaps the most interesting aspect of the system.”

Key inclusion criteria of the study included having more than 2 weeks since prior radiation or systemic therapy at time of leukapheresis; an absence of central nervous system lymphoma; and adequate pulmonary, cardiac, liver and renal function.

Key exclusion criteria included having a history of allogenic hematopoietic stem cell transplantation, uncontrolled incurrent illness, and other active malignancies, active hepatitis B or C infection, and a history of autoimmune disease with requirement of immunosuppressive medication within 6 months of treatment initiation.

Clinical trials evaluating LMY-920 in B-cell related multiple myeloma and systemic lupus erythematosus are ongoing. Additionally, an allogenic version of the BAFF CAR-T cell inhibitor is being developed.

Caimi P, Spear MA, Liter J, Largaespada D, Webber BR, Moriarity BS. Phase 1 study of novel transposon-based BAFF CAR-T cells (LMY-920) for treatment of relapsed or refractory NHL. 

 Published online November 5, 2024. doi:10.1136/jitc-2024-SITC2024.0244

Transposon-engineered BAFF ligand–based CAR T cells (LMY-920) demonstrated promising efficacy and a tolerable safety profile in a phase 1 trial involving three patients with relapsed/refractory B-cell non-Hodgkin lymphoma. The trial reported a single grade 1 cytokine release syndrome event and no immune effector-cell associated neurotoxicity syndrome. One patient achieved a complete response, while others showed mixed responses or stable disease. The study aimed to determine the recommended phase 2 dose and assess secondary endpoints like toxicity and disease response. Further trials are ongoing for other B-cell related conditions.

Transposon-engineered BAFF ligand–based CAR T cells induced responses with a tolerable safety profile among 3 patients with relapsed/refractory B-cell NHL.

Transposon-Based BAFF CAR T Cells Show Early Efficacy, Safety in R/R Non-Hodgkin Lymphoma

Lenvatinib (Lenvima) plus pembrolizumab (Keytruda) demonstrated evidence of tumor responses in patients with stage III/IV or recurrent endometrial carcinoma regardless of mismatch repair–proficient (pMMR) status, histology, and prior adjuvant therapy, according to findings from an exploratory analysis of the phase 3 ENGOT-en9/LEAP-001 trial (NCT03884101) presented at the 

Topline results from the study reveal that as of the data cut-off date of October 2, 2023, 55.7% of patients treated with the lenvatinib combination achieved an objective response, including 50.6% of the pMMR population. Furthermore, the median duration of response (DOR) was 16.1 months (range, 1.0+-48.7+) and 23.2 months (1.0+-49.0+), for all-comers and the pMMR population, respectively.

“Clinically meaningful response rates were seen regardless of baseline characteristics including MMR status, histology, and prior adjuvant therapy,” Anna Dańska-Bidzińska, MD, a gynecologist from Warsaw Medical University in Warsaw, Poland, wrote in the presentation with study coinvestigators. “Patients who experienced a response to lenvatinib plus pembrolizumab, especially patients demonstrating a [complete response (CR)], had promising [progression-free survival (PFS)] and [overall survival (OS)].”

Additional data show a median time to objective response of 2.1 months (range, 1.3-26.4) and 2.1 months (1.2-26.4) among all-comers and pMMR patients, respectively. In each respective group, the median duration of treatment exposure for responders was 17.1 months (range, 1.5-48.4) and 19.8 months (1.5-51.5).

Furthermore, Kaplan-Meier PFS estimates by response in the pMMR population was 18.4 months (95% CI, 15.1-26.8) among all responders and 13.9 months (95% CI, 12.3-15.6) among patients with a partial response (PR), and for those with a CR it was not reached ([NR]; 95% CI, 29.1-NR). Among all-comers, it was 27.3 months (95% CI, 20.9-36.8), 15.1 months (95% CI, 12.9-19.4), and NR (95% CI, NR-NR) respectively.

Kaplan-Meier OS estimates by response in the pMMR population was 43.6 months (95% CI, 37.9- NR) among all responders, 37.6 months (95% CI, 30.9-NR) among patients with a PR, and NR (95% CI, 39.5-NR) for those with a CR. Among all-comers, it was NR (95% CI, 47.0-NR), 43.5 months (95% CI, 32.7-NR), and NR (95% CI, NR-NR), respectively.

The phase 3, multicenter, open-label study randomly assigned patients 1:1 with stage III to IV recurrent endometrial carcinoma to receive lenvatinib at 20 mg orally daily until disease progression plus pembrolizumab at 200 mg intravenously every 3 weeks until disease progression or 35 cycles. In the comparator arm, patients received paclitaxel at 175 mg/m

 intravenously plus carboplatin at area under the curve 6 intravenoulsy every 3 weeks for up to 7 cycles.

The study’s dual primary end points were PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. Secondary end points included objective response rate (ORR) per RECIST v1.1 by BICR, safety, and health-related quality of life. Exploratory end points included DOR per RECIST v1.1 by BICR.

Among responders in the lenvatinib combination group, all experienced adverse events (AEs). Any-grade and grade 3 or higher treatment-related AE (TRAE) occurrence was 99.1% and 82.5%, respectively. Discontinuation of lenvatinib, pembrolizumab, or both due to TRAEs occurred in 27.8%, 18.8%, and 3.4% of patients, respectively. Notably, a single treatment-related grade 5 instance of pneumonitis occurred.

“This exploratory analysis from the ENGOT-en9/LEAP-001 study provides evidence of substantial antitumor activity with lenvatinib plus pembrolizumab,” Dańska-Bidzińska and study coinvestigators concluded in the presentation. “Responses among patients in the lenvatinib plus pembrolizumab arm were both deep and durable…AEs among patients who experienced a CR or PR were manageable with dose modifications and supportive care.”

Dańska-Bidzińska A, Makker V, Salutari V, et al. Characterization of tumor responses with lenvatinib plus pembrolizumab in the ENGOT-en9/LEAP-001 study. Presented at the European Society for Medical Oncology (ESMO) Congress 2024. September 13-17, 2024; Barcelona, Spain. Abstract 737P.

Lenvatinib combined with pembrolizumab showed significant tumor response in patients with stage III/IV or recurrent endometrial carcinoma, irrespective of mismatch repair status, histology, or prior therapy. The phase 3 ENGOT-en9/LEAP-001 trial reported a 55.7% objective response rate, with a median duration of response of 16.1 months. Progression-free survival and overall survival were notably promising, especially in complete responders. Adverse events were prevalent but manageable. The study's findings underscore the combination's substantial antitumor activity and potential as a treatment option for this patient population.

Lenvatinib plus pembrolizumab led to tumor responses regardless of mismatch repair–proficient status, histology, and prior adjuvant therapy.

Roman Fabbricatore

Articles

First-Line FOLFIRINOX Fails to Improve OS vs First-Line NALIRIFOX in Metastatic PDAC

Evorpacept Plus TRP Generates Superior Antitumor Responses, Survival Outcomes in HER2+ Gastric/GEJ Cancer

Tamoxifen Reduces Ipsilateral Breast Recurrence in Good-Risk Ductal CIS

Transposon-Based BAFF CAR T Cells Show Early Efficacy, Safety in R/R Non-Hodgkin Lymphoma

Lenvatinib Plus Pembrolizumab Affords Deep and Durable Responses in Endometrial Cancer