Category: 3. Business

Pembrolizumab (Keytruda) in combination with weekly paclitaxel, with or without bevacizumab (Avastin), statistically significantly improved progression-free survival (PFS) regardless of PD-L1 status and overall survival (OS) in PD-L1–expressing tumors in patients with platinum-resistant recurrent ovarian cancer (PRROC). These findings came from the phase 3 ENGOT-ov65/KEYNOTE-B96 trial (NCT05116189) and were shared at the European Society of Medical Oncology (ESMO) Congress 2025.

The analysis was broken down between the population of patients with a combined positive score (CPS) of 1 or higher and the intention-to-treat population. Furthermore, data were broken down between interim analysis 1 (IA1), which had a data cutoff date of April 3, 2024, and interim analysis 2 (IA2), which had a data cutoff date of May 5, 2025.

The CPS of 1 or Higher Population

At IA1, the median PFS was 8.3 months (95% CI, 7.0-9.4) in the pembrolizumab arm compared with 7.2 months (95% CI, 6.2-8.1) in the placebo arm, with 12-month PFS rates of 35.2% (95% CI, 28.8%-41.7%) vs 22.6% (95% CI, 17.0%-28.7%), respectively (HR, 0.72; 95% CI, 0.58-0.89; P = .0014).

At IA2, the median PFS was 8.3 months in the pembrolizumab arm compared with 7.2 months in the placebo arm (HR, 0.75; 95% CI, 0.61-0.91); the 12-month PFS rates were 35.9% vs 23.9%, respectively, and the 18-month rates were 18.7% vs 10.5%.

The median OS was 18.2 months (95% CI, 15.3-21.0) in the pembrolizumab arm compared with 14.0 months (95% CI, 12.5-16.1) in the placebo arm, with 12-month OS rates of 69.1% vs 59.3%, and 18-month OS rates of 51.5% vs 38.9%, respectively (HR, 0.76; 95% CI, 0.61-0.94; P = .0053).

The objective response rate (ORR) was 53.0% (95% CI, 45.8%-60.0%), with a complete response (CR) rate of 9.9% and a partial response (PR) rate of 43.1%, in the pembrolizumab arm; in the placebo arm, the ORR was 46.6% (95% CI, 39.6%-53.7%), with a CR rate of 7.8% and a PR rate of 38.7%. The 12- and 18-month duration of response (DOR) rates in the pembrolizumab arm were 46.7% and 28.4% compared with 29.6% and 16.4% in the placebo arm.

The ITT Population

At IA1, the median PFS was 8.3 months (95% CI, 7.2-8.6) with pembrolizumab compared with 6.4 months (95% CI, 6.2-8.1) with placebo, with 12-month PFS rates of 33.1% (95% CI, 27.7%-38.5%) and 21.3% (95% CI, 16.6%-26.4%), respectively (HR, 0.70; 95% CI, 0.58-0.84; P <.0001).

At IA2, the median PFS was 8.3 months vs 6.4 months, respectively (HR, 0.73; 95% CI, 0.62-0.86); the 12-month PFS rates were 33.7% vs 22.5%, and the 18-month PFS rates were 17.3% vs 9.0%.

The ORR was 50.4% (95% CI, 44.3%-56.4%), with a CR rate of 8.3% and a PR rate of 42.0%, in the pembrolizumab arm; in the placebo arm, the ORR was 40.8% (95% CI, 35.0%-46.8%), with a CR rate of 6.0% and a PR rate of 34.8%.Furthermore, the 12- and 18-month DOR rates in the pembrolizumab arm were 46.6% and 26.5% compared with 28.4% and 14.5% in the placebo arm.

“These data support the use of pembrolizumab plus weekly paclitaxel, with or without bevacizumab, as a new standard of care for patients with PRROC,” presenting author Nicoletta Colombo, MD, PhD, of the Gynecologic Oncology Program at the European Institute of Oncology, IRCCS, in Milan, Italy, and the Department of Medicine and Surgery at the University of Milan-Bicocca in Italy, wrote with coauthors in the presentation.

Safety Analyses

Any-grade treatment-related adverse events (TRAEs) occurred in 97.8% of the pembrolizumab arm and 95.3% of the placebo arm; grade 3 or higher TRAEs occurred in 67.5% and 55.3%, respectively. TRAEs were serious in 33.1% and 19.5%, led to death in 0.9% and 1.6%, and led to discontinuation of any treatment in 35.9% and 28.0%.

Any-grade immune-mediated AEs occurred in 39.1% and 18.9%, and grade 3 or higher events occurred in 11.6% and 3.5%. They were serious events in 10.9% and 2.2%, and led to treatment discontinuation in 6.9% and 2.5%.

The most common TRAEs in both groups included anemia (49.7% vs 42.1%, respectively), peripheral neuropathy (38.8% vs 31.1%), alopecia (37.8% vs 34.0%), fatigue (35.3% vs 33.0%), and nausea (31.3% vs 27.4%). The most common immune-mediated AEs were hypothyroidism (17.8% vs 6.0%), infusion reactions (5.9% vs 4.7%), and hyperthyroidism (5.0% vs 0.6%).

Trial Breakdown

A total of 643 patients with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were enrolled in the trial and randomly assigned to either the pembrolizumab arm (n = 322) or the placebo arm (n = 321). Treatment was either pembrolizumab at 400 mg once every 6 weeks for 18 cycles or placebo on the same schedule; all patients received paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 3-week-long cycle, and they either did or did not receive bevacizumab at 10 mg/kg every 2 weeks.

Patients were enrolled in the trial if they had received 1 or 2 prior lines of therapy with at least 1 platinum-based chemotherapy; prior anti-PD-1 or anti-PD-L1 agents, PARP inhibitors, and bevacizumab were permitted. Additionally, patients had radiographic progression within 6 months after the last dose of platinum-based chemotherapy and an ECOG performance status of 0 or 1.

The primary end point of the trial was PFS per RECIST v1.1 by investigator assessment, and a key secondary end point was OS.

The median age of patients was 62 years vs 61 years in the pembrolizumab vs placebo arm, 64.3% and 67.6% of patients were White, 41.3% and 41.1% had a PD-L1 CPS from 1 to less than 10, and 31.4% and 31.2% had a PD-L1 CPS of at least 10.

Reference

Colombo N, Zsiros E, Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: Results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study. Presented at: European Society of Medical Oncology Congress 2025; October 17–20, 2025; Berlin, Germany. Abstract LBA3.

Adjuvant treatment with cemiplimab-rwlc (Libtayo) was associated with a similar incidence of second primary tumors (SPTs) compared with placebo in patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery and postoperative radiotherapy, according to findings from an analysis of the phase 3 C-POST trial (NCT03969004) presented at the 2025 ESMO Congress.¹

During the treatment period, the proportion of patients who developed at least one SPT was 11% in the cemiplimab arm (n = 209) compared with 12% in the placebo arm (n = 206); during the study’s follow-up period, these rates were 8% and 7%, respectively. During the treatment period, the cumulative number of SPTs was 32 with cemiplimab vs 82 for placebo, corresponding to annualized, adjusted annualized SPT rates of 1.23 (95% CI, 0.60-2.54) and 2.81 (95% CI, 1.23-6.45), respectively. In the follow-up period, 36 total SPTs occurred in the cemiplimab arm vs 41 in the placebo arm, and the annualized SPT rates were 0.72 (95% CI, 0.30-1.71) and 1.17 (95% CI, 0.40-3.49), respectively.

During the treatment period, 9% of patients in the cemiplimab arm had 1 SPT, 1% had 2 SPTs, less than 1% had 3 SPTs, 0% had 4 SPTs, less than 1% had 5 SPTs, and 0% had 6 or more SPTs. In the placebo arm, these rates were 8%, 2%, less than 1%, less than 1%, 0%, and 1%, respectively. Incidence was similar during the follow-up period, with 4% of patients in each arm experiencing 1 SPT and less than 1% of patients falling into the multiple SPT groups within each arm.

In a post hoc analysis incorporating the first occurrence of SPTs alongside disease-free survival (DFS) events (recurrence or death), efficacy continued to favor cemiplimab over placebo (HR, 0.43; 95% CI, 0.30-0.60). The median DFS in this analysis was not reached (NR; 95% CI, not evaluable [NE]-NE) in the cemiplimab group vs 21.7 months (95% CI, 12.9-39.2) in the placebo group. At 24 months, DFS rates were 81.1% with cemiplimab vs 59.1% with placebo, and this benefit was maintained over time, with rates of 73.4% vs 48.7% at 36 months and 68.4% vs 41.5% at 48 months, respectively.

“The lower number of SPTs in the cemiplimab arm appeared to be driven by a small number of patients with multiple SPTs observed in the placebo arm. The robust [DFS] efficacy signal with cemiplimab vs placebo was maintained in a post hoc analysis in which SPTs were included as [DFS] events,” Danny Rischin, MD, who serves as the director of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, noted in the conclusion of his presentation. “These prospective, randomized data suggest that there may be a subset of patients who experience fewer SPTs with cemiplimab, although further investigation is required.”

What Was Established in the Primary Analysis of the C-POST Trial?

With a median follow-up of 24 months (range, 2-64), previously reported findings from the primary analysis showed that patients who received adjuvant cemiplimab after surgical resection and postoperative radiotherapy achieved a median DFS that was NR (95% CI, NE-NE) compared with 49.4 months (95% CI, 48.5-NE) among those treated with placebo (n = 206; HR, 0.32; 95% CI, 0.20-0.51; P < .001). The estimated 24-month DFS rates were 87.1% (and 64.1%, respectively.

Based on those findings, on October 8, 2025the FDA approved cemiplimab for the adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation.² Following this decision, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the agent’s use in the same indication.³

What Was the Design of the C-POST Trial and the Post Hoc Analysis?

The phase 3 C-POST trial is a randomized, double-blind, placebo-controlled study designed to evaluate adjuvant cemiplimab in patients with histologically confirmed CSCC who had undergone complete resection with curative intent and completed postoperative radiotherapy.¹ Patients were required to have high-risk features, which included nodal extracapsular extension with at least one lymph node measuring 20 mm or more, or three or more involved lymph nodes; in-transit metastases; perineural invasion; T4 lesions; or recurrent CSCC with 1 or more additional high-risk characteristics.

Participants were randomly assigned 1:1 to receive cemiplimab or placebo. In part 1 of the study, patients received cemiplimab at 350 mg intravenously every 3 weeks for 12 weeks, followed by cemiplimab at 700 mg every 6 weeks for an additional 36 weeks. Those in the control group received matched placebo on the same schedule. Treatment continued until completion of the planned duration, disease recurrence, or unacceptable toxicity.

Patients who experienced recurrence after completing placebo treatment or after at least three months following cemiplimab completion were eligible to enter an optional open-label extension phase (part 2) to receive cemiplimab at 350 mg every 3 weeks for up to 96 weeks.

The primary end point of the trial was DFS. Key secondary end points include freedom from locoregional recurrence, freedom from distant recurrence, cumulative occurrence of second primary tumors, overall survival, and safety.

The median age of patients was 71.0 years (range, 33-87) in the cemiplimab group and 70.5 years (range, 36-95) in the placebo group. Most patients were 65 years of age or older, representing 73% and 68% of each respective arm. The majority of participants were male (83% in both arms) and White (90% vs 92%).

Geographically, 43% of patients in the cemiplimab arm and 44% in the placebo arm were enrolled from Australia or New Zealand, 18% and 15% were from North America, and 39% and 41% were from the rest of the world.

Most patients had resected high-risk tumors located in the head and neck region (79% in the cemiplimab group vs 86% in the placebo group), and 21% and 14% had non–head and neck tumors, respectively. Regarding risk classification, 60% of patients in the cemiplimab arm and 57% in the placebo arm were categorized as having nodal high-risk disease; 40% and 43%, respectively, had non-nodal high-risk features.

Disclosures: Rischin reported receiving institutional research funding from ALX Oncology, AstraZeneca, Bicara Therapeutics, Decibel Therapeutics, Erasca, Marck, and Regeneron Pharmaceuticals; and having uncompensated relationships with Eisai, GSK, Merck, and Regeneron Pharmaceuticals.

References

1. Rischin D, Porceddu S, Day F, et al. Analysis of second primary CSCC tumors (SPTs) reported during the C-POST trial, a randomized phase 3 study of adjuvant cemiplimab vs placebo for high-risk CSCC. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 1603MO.
2. FDA approves cemiplimab-rwlc for adjuvant treatment of cutaneous squamous cell carcinoma. FDA. October 8, 2025. Accessed October 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-adjuvant-treatment-cutaneous-squamous-cell-carcinoma
3. Libtayo (cemiplimab) recommended for EU approval by the CHMP for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC) with a high risk of recurrence after surgery and radiation. News release. Regeneron. October 17, 2025. Accessed October 18, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-recommended-eu-approval-chmp-adjuvant

Treatment with tarlatamab-dlle (Imdelltra) improved overall survival (OS) vs chemotherapy among patients with small cell lung cancer (SCLC) regardless of chemotherapy-free intervals (CFIs) or prior receipt of anti–PD-(L)1 therapy, according to data from the phase 3 DeLLphi-304 trial (NCT05740566) presented at the European Society for Medical Oncology (ESMO) Congress 2025.¹

The median OS was 10.9 months in the tarlatamab arm vs 6.4 months in the chemotherapy arm among patients with a CFI of less than 90 days (HR, 0.60; 95% CI, 0.43-0.84). The 12-month OS rates in this population were 40% vs 24% with tarlatamab and chemotherapy, respectively.

Among patients with a CFI of 90 days or longer, the median OS was 17.1 months compared with 10.6 months in each arm, with respective 12-month OS rates of 64% and 48% (HR, 0.65; 95% CI, 0.45-0.93). Regarding patients with disease progression within 2 weeks of their most recent platinum-containing treatment, the Kaplan-Meier estimated 6-month OS rates were 55% with tarlatamab and 35% with chemotherapy.

Among patients with prior receipt of anti–PD-(L)1 agents, the median OS was 14.1 months in the tarlatamab arm and 8.3 months in the chemotherapy arm; the respective 12-month OS rates were 53% vs 36% (HR, 0.61; 95% CI, 0.45-0.82). In the group of patients without prior anti–PD-(L)1 therapy, the median OS was 13.6 months vs 8.3 months, and the 12-month OS rates were 53% vs 40% (HR, 0.65; 95% CI, 0.42-1.03). Overall, data showed that prior exposure to anti–PD-(L)1 agents did not affect OS benefits with tarlatamab vs chemotherapy.

“In the second line, standard chemotherapies have demonstrated modest survival benefits, especially [in] those patients with platinum-resistant disease, [who] often have a poor prognosis. DeLLphi-304 is the first randomized phase 3 trial to demonstrate superior OS with tarlatamab compared with standard chemotherapy. Importantly, this survival benefit extended to patients with platinum-resistant disease,” presenting author Pedro F. Simoes da Rocha, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain, stated in the presentation.¹ “These findings reinforce the use of tarlatamab as a standard of care in second-line SCLC, including those patients with worse prognosis, such as [those] with platinum-resistant disease.”

In the randomized DeLLphi-304 trial, 509 patients were assigned 1:1 to receive tarlatamab (n = 254) or investigator’s choice of chemotherapy (n = 255), which included options of topotecan (n = 185), lurbinectedin (Zepzelca; n = 47), and amrubicin (n = 23). Investigators stratified patients by prior receipt of anti–PD-(L)1 agents, CFI interval, presence of brain metastases, and intended chemotherapy.

The trial’s primary end point was OS. Secondary end points included progression-free survival, patient-reported outcomes, objective response rate, and safety.

Patients with histologically or cytologically confirmed SCLC, disease progression following frontline platinum-based chemotherapy with or without anti–PD-(L)1 therapy, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Those with asymptomatic, treated, or untreated brain metastases were able to enroll.

In the tarlatamab and chemotherapy arms, respectively, 43% and 45% of patients had a CFI of less than 90 days, and 57% and 55% had a CFI of 90 days or longer. Additionally, 71% of patients in both arms had prior receipt of anti–PD-(L)1 therapy, while 29% from both arms did not. Investigators noted that subgroup baseline characteristics appeared to be balanced between treatment arms.

Across the different CFI and anti–PD-(L)1 subgroups, rates of grade 3 or higher treatment-related adverse effects (AEs) ranged from 24% to 30% in the tarlatamab arm and 58% to 69% in the chemotherapy arm. Any-grade events of cytokine release syndrome (CRS) occurred in 51% to 59% of patients who received tarlatamab across various subgroups, and subgroup status did not impact the risk of CRS.

Previously, the FDA granted accelerated approval to tarlatamab as a treatment for patients with extensive-stage SCLC following progression on prior platinum-based chemotherapy in May 2024.² Supporting data for this indication came from the phase 2 DELLphi-301 trial (NCT05060016).

References

1. Rocha P, Sun L, Cho BC, et al. Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): Outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase 3 DeLLphi-304 trial. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. LBA101.
2. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. May 16, 2024. Accessed October 18, 2024. https://tinyurl.com/48k34rw5