Tim Cortese

The Beamion LUNG-1 study showed that first-line Hernexeos had benefit for patients with HER2-mutated NSCLC.

Among patients with untreated, advanced HER2-mutated non-small cell lung cancer (NSCLC), treatment with Hernexeos (zongertinib) was associated with a significant and clinically meaningful benefit, clinical trial results have shown.

Results from the phase 1 Beamion LUNG-1 trial were presented at the European Society for Medical Oncology Congress 2025.

The objective response rate (ORR) was 77%, with a complete response rate of 8% and a partial response rate of 69%. The disease control rate was 96% with a stable disease rate of 19% and a progressive disease rate of 1%.

Objective Response Rate (ORR): the percentage of patients whose cancer shrinks (partial response) or disappears (complete response) after treatment. 

Disease Control Rate (DCR): the percentage of patients whose cancer either shrinks, disappears or stops growing for a period of time after treatment.

Duration of Response (DoR): how long a cancer continues to stay smaller or gone after it first responds to treatment.

Progression-Free Survival (PFS): the length of time during and after treatment that the cancer does not get worse.

ECOG Performance Status: a scale doctors use to describe how well a person can do daily activities. It ranges from 0 (fully active) to 5 (dead).

Interstitial Lung Disease / Pneumonitis: a group of conditions that cause inflammation and scarring in the lungs, sometimes as a side effect of cancer treatment. 

Alanine Aminotransferase (ALT) Increased: a higher-than-normal level of an enzyme called ALT in the blood, which may be a sign of liver irritation or damage.

Aspartate Aminotransferase (AST) Increased: a higher-than-normal level of an enzyme called AST in the blood, which can also suggest liver irritation or damage.

The median time to objective response was 1.4 months, and at the time of data cutoff, 47% of patients remained on treatment.

The median follow-up for duration of response (DOR) was 9.7 months, and the six-month DOR rate was 80%. The median follow-up for progression-free survival (PFS) was 11.6 months, and the six-month PFS rate was 79%.

“[Hernexeos] given as a first-line therapy demonstrated significant and clinically meaningful benefit in treatment-naïve patients with advanced 

-mutant NSCLC,” Sanjay Popat, consultant medical oncologist, head of the Lung Unit, and lead for the Lung Cancer Research Programme at The Royal Marsden NHS Foundation Trust, stated during the presentation.

A total of 74 patients were given 120 mg of Hernexeos. Of note, two patients had received prior treatment. The presentation focused on cohort 2, which enrolled patients who were treatment-naïve and had a tyrosine kinase domain (TKD) mutation.

Patients were included if they were 18 years or older with advanced/metastatic non-squamous HER2-mutated NSCLC with one or more measurable non-central nervous system lesions, and an ECOG performance status of 0 or 1. Additionally, patients who had stable/asymptomatic brain metastases were eligible for treatment.

The median patient age was 67 years, 40% of patients were between 65 and 74 years old, and 18% were 75 years or older. Additionally, 46% of patients were Asian compared with 45% who were not, 64% of patients had never used tobacco, 30% had brain metastases, and 66% had A775_G776insYVMA.

Regarding safety, 91% of patients reported treatment-related side effects, with 18% reporting a grade 3 (severe) treatment-related side effect. No grade 4 (life-threatening) or 5 (fatal) treatment-related side effects were reported. A total of 15% of patients had side effects leading to dose reductions, and 9% had side effects leading to discontinuation. There were two cases of interstitial lung disease/pneumonitis, both of which were grade 2.

The most common TRAEs included diarrhea (54%), rash (23%), alanine aminotransferase increased (18%), aspartate aminotransferase increased (16%), dysgeusia (16%), and nausea (16%). Popat noted that the safety profile remained consistent with previously reported data. Additionally, there was a low incidence of grade 3 or higher side effects.

In August 2025, the FDA gave accelerated approval to

Hernexeos for patients with previously treated metastatic or unresectable non-squamous NSCLC who had HER2 TKD activating mutations, as detected by an FDA-approved test.

“Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG-1,” by Sanjay Popat, et al. Presented at the European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA74.

“FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations,” FDA; https://tinyurl.com/bdh2d4uc

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Articles

Hernexeos (zongertinib) has shown significant clinical benefits in untreated, advanced HER2-mutated NSCLC patients, with a 77% objective response rate and a 96% disease control rate. The phase 1 Beamion LUNG-1 trial reported a median time to response of 1.4 months and a six-month progression-free survival rate of 79%. The trial included 74 patients, with a median age of 67, and demonstrated a favorable safety profile, with 91% experiencing treatment-related side effects, primarily grade 1 or 2. The FDA granted accelerated approval for Hernexeos in August 2025.

The Beamion LUNG-1 study showed that first-line Hernexeos had benefit for patients with HER2-mutated NSCLC. 

Hernexeos Effective in HER2-Mutated NSCLC

Loqtorzi improved progression-free and overall survival versus chemotherapy in HER2-expressing advanced urothelial cancer.

Loqtorzi (disitamab vedotin plus toripalimab-tpzi) demonstrated a statistically significant improvement in survival compared with standard-of-care chemotherapy as a frontline treatment for patients with HER2-expressing locally advanced or metastatic urothelial carcinoma, according to results from a phase 3 study shared at the 

With a median survival follow-up of 18.2 months and a data cutoff date of March 31, 2025, the median progression-free survival per blinded independent review committee was 13.1 months with Loqtorzi compared with 6.5 months with chemotherapy, representing a 64% reduction in the risk of progression or death. The 12- and 18-month progression-free survival rates with Loqtorzi were 54.5% and 38.4%, respectively, versus 16.2% and 7.5% with chemotherapy.

The median overall survival was 31.5 months in the Loqtorzi arm compared with 16.9 months in the chemotherapy arm, correlating with a 46% reduction in the risk of death. The 12-, 18-, and 24-month overall survival rates in the Loqtorzi arm were 79.5%, 64.6%, and 52.8%; in the chemotherapy arm, these rates were 62.5%, 48.1%, and 39.4%.

The progression-free survival and overall survival benefits were consistent across all prespecified subgroups.

In the Loqtorzi arm, the overall response rate per blinded independent review committee was 76.1%, with complete responses in 4.5% and partial responses in 71.6% of patients; in the chemotherapy arm, the overall response rate was 50.2%, with complete responses in 1.2% and partial responses in 49%. The investigator-assessed overall response rate with Loqtorzi was 71.6%, with complete responses in 4.1% and partial responses in 67.5% of patients compared with a 49.8% overall response rate with chemotherapy, comprising complete responses in 3.3% and partial responses in 46.5% of patients.

Progression-free survival (PFS): time during and after treatment that a patient lives without cancer growing or spreading.

Overall survival (OS): time from treatment start until death from any cause.

Overall response rate (ORR): percentage of patients whose cancer shrinks or disappears after treatment.

Complete response (CR): disappearance of all signs of cancer.

Partial response (PR): significant shrinkage of cancer but not complete disappearance.

Duration of response (DOR): length of time treatment keeps cancer under control after first response.

Disease control rate (DCR): percentage of patients who achieve complete response, partial response, or stable disease.

The median duration of response per blinded independent review committee was 14.6 months with Loqtorzi compared with 5.6 months with chemotherapy. In the Loqtorzi arm, the six-, 12-, and 18-month duration of response rates were 78.9%, 58.5%, and 42.4%; in the chemotherapy arm, these rates were 37.2%, 19%, and 8.7%.

“The phase 3 study demonstrated for the first time superiority of an anti-HER2 antibody-drug conjugate plus an anti–programmed cell death protein 1 inhibitor in a biomarker-selected patient population with locally advanced and metastatic urothelial cancer,” lead study author Jun Guo, of the Key Laboratory of Carcinogenesis and Translational Research in the Department of Melanoma and Sarcoma at Peking University Cancer Hospital and Institute in Beijing, China, said in the presentation. “Loqtorzi offers a valuable new treatment option and represents a new standard of care for the first-line treatment of patients with HER2-expressing locally advanced or metastatic urothelial cancer.”

The open-label study randomly assigned 484 patients one-to-one to receive either Loqtorzi (243 patients) or gemcitabine plus cisplatin/carboplatin (241 patients). Treatment consisted of two mg/kg of intravenous Loqtorzi and three milligrams per kilogram (mg/kg) of toripalimab every two weeks, or gemcitabine at 1000 mg/m2 on day one and day eight and cisplatin at 70 milligrams per sqaure meter (mg/m2) on day one or carboplatin at area under curve 4.5 on day one every three weeks. There was no maximum number of cycles set for Loqtorzi, and the maximum number of chemotherapy cycles was six.

Eligible patients had no prior systemic treatment for unresectable locally advanced or metastatic urothelial cancer and central lab-confirmed HER2 immunohistochemistry of 1+, 2+, or 3+; patients were eligible for cisplatin or carboplatin, had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and had an Eastern Cooperative Oncology Group performance status of 0 or 1.

The primary end points were progression-free survival per blinded independent review committee and overall survival. Secondary end points included progression-free survival by investigators, overall response rate, disease control rate, duration of response, safety, and quality of life.

Subsequent systemic anticancer treatment was received by 27.2% of patients on the Loqtorzi arm and 64.7% of the chemotherapy arm; this included anti–HER2-containing therapy in 2.1% and 40.2%, respectively, programmed cell death protein 1/programmed cell death ligand 1 inhibitor therapy in 10.7% and 50.2%, and both in 0.8% and 31.1%.

Regarding safety, treatment-emergent side effects occurred in 100% of patients across both arms, and treatment-related side effects occurred in 98.8% of patients on the Loqtorzi arm and 100% of those on the chemotherapy arm. Grade 3 (severe) or higher treatment-related side effects occurred in 55.1% and 86.9% of patients, respectively; grade 3, 4 (life-threatening), and 5 (death) side effects were observed in 44%, 9.9%, and 1.2% of those on the experimental arm versus 41.9%, 43.7%, and 1.4% of the chemotherapy arm. Treatment-related side effects led to discontinuation in 12.3% versus 10.4%, respectively. Any-grade and grade 3 or higher immune-related side effects occurred in 46.9% and 18.9% of the Loqtorzi arm.

“Loqtorzi versus chemotherapy in first-line locally advanced or metastatic urothelial carcinoma with HER2 expression” by Dr. Sheng X, et al., 2025 European Society of Medical Oncology Congress.

“Loqtorzi in HER2-expressing advanced urothelial cancer” by Dr. Sheng X, et al., New England Journal of Medicine.

Loqtorzi, a combination of disitamab vedotin and toripalimab-tpzi, significantly improved survival outcomes compared to standard chemotherapy in HER2-expressing advanced urothelial carcinoma. The phase 3 study showed a median progression-free survival of 13.1 months with Loqtorzi versus 6.5 months with chemotherapy, and a median overall survival of 31.5 months versus 16.9 months. The overall response rate was higher in the Loqtorzi arm, with a longer median duration of response. Safety profiles indicated a high incidence of treatment-related side effects, though severe side effects were less frequent with Loqtorzi.

Loqtorzi Extends Survival in HER2-Positive Advanced Urothelial Cancer

Clinical trial results showed favorable results with Keytruda-based therapy in this ovarian cancer population.

Among patients with platinum-resistant recurrent ovarian cancer (PRROC), the treatment combination of Keytruda (pembrolizumab) with weekly paclitaxel with or without Avastin (bevacizumab) was associated with significant improvements in progression-free survival (PFS) regardless of PD-L1 status and overall survival (OS), clinical trial results have shown.

Findings from the phase 3 ENGOT-ov65/KEYNOTE-B96 trial were shared at the European Society of Medical Oncology 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.

Progression-Free Survival (PFS): the length of time a patient lives with a disease without it getting worse or spreading.

Overall Survival (OS): the length of time, usually measured from the start of diagnosis or treatment, that a patient is still alive.

Combined Positive Score (CPS): a way to measure the amount of PD-L1 protein, which can affect treatment decisions, found on both cancer cells and certain immune cells in a tumor sample.

Objective Response Rate (ORR): the percentage of patients whose cancer significantly shrinks or disappears after a specific treatment.

Complete Response (CR): the disappearance of all signs of cancer following treatment, though it does not always mean the cancer is cured.

Partial Response (PR): a decrease in the size or amount of cancer in the body by a specific amount, usually 30%, following treatment.

Anemia: a condition where the body doesn't have enough healthy red blood cells to carry adequate oxygen to the body's tissues.

Peripheral Neuropathy: nerve damage in the hands and feet that can cause symptoms like pain, tingling, numbness, or muscle weakness.

Alopecia: the temporary or permanent loss of hair from the head or other parts of the body, often a side effect of chemotherapy or radiation.

ECOG Performance Status: a scale, ranging from 0 (fully active) to 5 (dead), used by doctors to assess how a patient's disease is affecting their daily activities and physical well-being.

At IA1, the median PFS was 8.3 months in the Keytruda arm compared with 7.2 months in the placebo arm, with 12-month PFS rates of 35.2% versus 22.6%, respectively.

At IA2, the median PFS was 8.3 months in the Keytruda arm compared with 7.2 months in the placebo arm; the 12-month PFS rates were 35.9% versus 23.9%, respectively, and the 18-month rates were 18.7% versus 10.5%.

The median OS was 18.2 months in the Keytruda arm compared with 14 months in the placebo arm, with 12-month OS rates of 69.1% versus 59.3%, and 18-month OS rates of 51.5% versus 38.9%, respectively.

The objective response rate (ORR) was 53% with a complete response (CR) rate of 9.9% and a partial response (PR) rate of 43.1%, in the Keytruda arm; in the placebo arm, the ORR was 46.6%, 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 Keytruda arm were 46.7% and 28.4% compared with 29.6% and 16.4% in the placebo arm.

At IA1, the median PFS was 8.3 months with Keytruda compared with 6.4 months with placebo, with 12-month PFS rates of 33.1% and 21.3%, respectively.

At IA2, the median PFS was 8.3 months versus 6.4 months, respectively; the 12-month PFS rates were 33.7% versus 22.5%, and the 18-month PFS rates were 17.3% versus 9%.

The ORR was 50.4%, with a CR rate of 8.3% and a PR rate of 42%, in the Keytruda arm; in the placebo arm, the ORR was 40.8%, with a CR rate of 6% and a PR rate of 34.8%.Furthermore, the 12- and 18-month DOR rates in the Keytruda arm were 46.6% and 26.5% compared with 28.4% and 14.5% in the placebo arm.

“These data support the use of [Keytruda] plus weekly paclitaxel, with or without [Avastin], as a new standard of care for patients with PRROC,” presenting author Dr. Nicoletta Colombo 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.

Any-grade treatment-related side effects occurred in 97.8% of the Keytruda arm and 95.3% of the placebo arm; grade 3 (severe) or higher treatment-related side effects occurred in 67.5% and 55.3%, respectively. Treatment-related side effects 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%.

Any-grade immune-mediated side effects 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 treatment-related side effects in both groups included anemia (49.7% versus 42.1%, respectively), peripheral neuropathy (38.8% versus 31.1%), alopecia (37.8% versus 34%), fatigue (35.3% versus 33%) and nausea (31.3% versus 27.4%). The most common immune-mediated side effects were hypothyroidism (17.8% versus 6%), infusion reactions (5.9% versus 4.7%) and hyperthyroidism (5% versus 0.6%).

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 Keytruda arm (322 patients) or the placebo arm (321 patients). Treatment was either Keytruda at 400 mg once every six weeks for 18 cycles or placebo on the same schedule; all patients received paclitaxel at 80 mg/m

 on days 1, 8, and 15 of each three-week-long cycle, and they either did or did not receive Avastin at 10 mg/kg every 2 weeks.

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

The median age of patients was 62 years versus 61 years in the Keytruda versus 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. 

"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," by Dr. Nicoletta Colombo. Presented at: European Society of Medical Oncology Congress 2025; October 17–20, 2025; Berlin, Germany. Abstract LBA3.

The combination of Keytruda (pembrolizumab) with weekly paclitaxel, with or without Avastin (bevacizumab), significantly improved progression-free survival (PFS) and overall survival (OS) in patients with platinum-resistant recurrent ovarian cancer (PRROC), regardless of PD-L1 status. The phase 3 ENGOT-ov65/KEYNOTE-B96 trial demonstrated these benefits in both the combined positive score (CPS) ≥1 and intention-to-treat populations. Safety analyses revealed high rates of treatment-related side effects, with notable differences in immune-mediated events. These findings suggest a potential new standard of care for PRROC patients.

Keytruda Combo Improves Progression, Survival in Recurrent Ovarian Cancer

Clinical trial data support the use of Imdelltra as a standard of care for all patients with second-line small cell lung cancer.

Among patients with small cell lung cancer (SCLC), treatment with Imdelltra (tarlatamab-dlle) was found to improve overall survival (OS) when compared with chemotherapy, regardless of chemotherapy-free interviews (CFIs) or prior administration of anti-PD-(L)1 therapy, trial results have shown.

Data from the phase 3 DeLLphi-304 trial were presented at the European Society for Medical Oncology 2025 Congress in Berlin.

The median OS was 10.9 months in the Imdelltra arm versus 6.4 months in the chemotherapy arm among patients with a CFI of less than 90 days. The 12-month OS rates in this population were 40% versuus 24% with Imdelltra 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. Regarding patients with disease progression within two weeks of their most recent platinum-containing treatment, the Kaplan-Meier estimated six-month OS rates were 55% with Imdelltra and 35% with chemotherapy.

Among patients with prior receipt of anti–PD-(L)1 agents, the median OS was 14.1 months in the Imdelltra arm and 8.3 months in the chemotherapy arm; the respective 12-month OS rates were 53% versus 36%. In the group of patients without prior anti–PD-(L)1 therapy, the median OS was 13.6 months versus 8.3 months, and the 12-month OS rates were 53% versus 40%. Overall, data showed that prior exposure to anti–PD-(L)1 agents did not affect OS benefits with Imdelltra 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 [Imdelltra] compared with standard chemotherapy. Importantly, this survival benefit extended to patients with platinum-resistant disease,” presenting author Dr. Pedro F. Simoes da Rocha, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain, stated in the presentation. “These findings reinforce the use of [Imdelltra] 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 to receive Imdelltra (254 patients) or investigator’s choice of chemotherapy (255 patients), which included options of topotecan (185 patients), lurbinectedin (47 patients) and amrubicin (23 patients). Investigators stratified patients by prior receipt of anti–PD-(L)1 agents, CFI interval, presence of brain metastases and intended chemotherapy.

In the Imdelltra 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 (severe) or higher treatment-related side effects ranged from 24% to 30% in the Imdelltra 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 Imdelltra across various subgroups, and subgroup status did not impact the risk of CRS.

The FDA granted accelerated approval toImdelltra as a treatment for patients with extensive-stage SCLC following progression on prior platinum-based chemotherapy in May 2024. Supporting data for this indication came from the phase 2 DELLphi-301 trial.

“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” by Dr. Pedro F. Simoes da Rocha et al., presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. LBA101.

“FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer,” news release. https://tinyurl.com/48k34rw5

Imdelltra (tarlatamab-dlle) has demonstrated improved overall survival (OS) in small cell lung cancer (SCLC) patients compared to chemotherapy, regardless of chemotherapy-free intervals (CFIs) or prior anti-PD-(L)1 therapy. The phase 3 DeLLphi-304 trial showed significant OS benefits, with Imdelltra achieving higher 12-month OS rates across various subgroups, including those with platinum-resistant disease. The trial also highlighted a lower incidence of severe treatment-related side effects with Imdelltra. These findings support Imdelltra as a standard second-line treatment for SCLC, especially in patients with poor prognosis.

Tim Cortese

Hernexeos Effective in HER2-Mutated NSCLC

Loqtorzi Extends Survival in HER2-Positive Advanced Urothelial Cancer

Keytruda Combo Improves Progression, Survival in Recurrent Ovarian Cancer

Imdelltra Improves Survival For Some With Small Cell Lung Cancer

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