Ariana Pelosci

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

Enhertu plus Perjeta improved progression-free survival versus THP in patients with HER2-positive advanced or metastatic breast cancer across subgroups.

A clinically meaningful progression-free survival (PFS) benefit was observed with Enhertu (fam-trastuzumab deruxtecan-nxki) plus Perjeta (pertuzumab), despite prior treatment, hormone receptor status, or PIK3CA mutations, when compared versus Taxol, trastuzumab and Perjeta (THP), for patients with HER2-positive advanced or metastatic breast cancer. The results were presented as a subgroup analysis for the phase 3 trial at the 

What was the DESTINY-Breast09 Study Prior Treatment Status?

The PFS assessment for prior treatment status looked at those with de novo disease or recurrent disease. The median PFS for patients with de novo disease and treated with Enhertu plus Perjeta was not calculable (NC) compared versus 31.2 months for patients treated with THP. The PFS for those with recurrent disease in the Enhertu plus Perjeta arm was 38 months and 22.5 months for those in the THP arm.

The confirmed objective response rate (cORR) for patients with de novo disease receiving Enhertu plus Perjeta (200 patients) was 90.5% with 16.5% of patients having a complete response (CR) and 74% having a partial response (PR) versus 82% in the THP arm (200 patients) and 6.5% having a CR and 75.5% having a PR. For those with recurrent disease, the cORR for those with de novo disease (183 versus 187) was 79.2% with 13.7% having a CR and 65.6% having a PR versus a cORR of 74.9% with 10.7% having a CR and 64.2% having a PR.

The median duration of response (DOR) for de novo disease in the Enhertu plus Perjeta arm was 39.2 months versus 31.3 months for those in the THP arm. For those with recurrent disease, the median DOR was 35.3 months versus 21.9 months in the THP arm.

Baseline characteristics for those with de novo disease in the Enhertu plus Perjeta arm compared versus the THP arm was an ECOG performance status of zero (68% versus 60.5%), brain metastases (5% versus 3.5%), visceral metastases (73% versus 68.5%), hormone receptor positive status (56% versus 53%), and PIK3CA mutations not detected (73% versus 72.5%). For those with recurrent disease, the characteristics included an ECOG performance status of zero (65.6% versus 66.8%), brain metastases (8.2% versus 8%), visceral metastases (73.8% versus 70.1%), hormone receptor positive status (51.9% versus 55.1%), and PIK3CA mutations not detected (65.6% versus 64.7%).

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

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

Confirmed objective response rate (cORR): percentage of patients with a confirmed partial or complete response to treatment.

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

Partial response (PR): decrease in the size of the tumor or extent of cancer in the body after treatment.

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

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

PFS-2: time from randomization until second disease progression or death, whichever occurs first.

For those with de novo or recurrent disease, any treatment-emergent side effects occurred in 100% versus 99.4% of patients in the Enhertu arm versus 99% versus 98.9% in the THP arm. Side effects of grade 3 or higher were noted in 57% versus 52.5% in the Enhertu arm and 51% versus 53.8% in the THP arm. Any side effects leading to discontinuation occurred in 23% versus 18.2% of patients in the Enhertu arm versus 33.3% versus 22.8% in the THP arm. Adjudicated drug-related interstitial lung disease (ILD)/pneumonitis occurred in 14.5% versus 9.4% in the Enhertu arm and 1% versus 1.1% in the THP arm.

The median PFS for patients who were hormone receptor-positive was 38 months in the Enhertu plus Perjeta arm and 27.7 months for patients in the THP arm. For patients who were hormone receptor-negative, the median PFS in the Enhertu plus Perjeta arm was 40.7 months versus 22.6 months in the THP arm.

“Patients with [hormone receptor-positive disease] could receive concurrent [endocrine therapy] benefit after six cycles of Enhertu or discontinuation of Taxol [therapy], which occurred in 13.5% [of patients in the Enhertu plus Perjeta arm] versus 38.3% [in the THP arm],” Dr. Sibylle Loibl, chair of the German Breast Group and the Chief Executive Officer, and associate professor of obstetrics and gynecology at the Goethe University of Frankfurt, said in the presentation.

Regarding cORR for patients with hormone receptor-positive disease in the Enhertu plus Perjeta arm (207 patients) was 81.2%, with 14.5% of patients having a CR and 66.7% having a PR. In the THP arm (209 patients), the cORR was 77% with 7.2% of patients having a CR and 69.9% having a PR. For patients with hormone receptor-negative disease, the cORR in the Enhertu plus Perjeta arm (176 patients) was 89.8%, with 15.9% of patients having a CR and 73.9% having a PR. In the THP arm (178 patients), the cORR was 80.3% with 10.1% of patients having a CR and 70.2% having a PR.

The median DOR for patients with hormone receptor-positive disease receiving Enhertu plus Perjeta was 35.3 months versus 26.4 months for patients in the THP arm. For those with hormone receptor-negative disease, the median DOR in the Enhertu plus Perjeta arm was 39.2 months versus 26.3 months in the THP arm.

Baseline characteristics for patients who are hormone receptor-positive in the Enhertu plus Perjeta versus THP arms included an ECOG performance status of zero (68.1% versus 61.7%), brain metastases (4.8% versus 3.3%), visceral metastases 71% versus 67.5%), de novo disease (54.1% versus 50.7%), and PIK3CA mutations not detected (70.5% versus 69.4%). For patients who are hormone receptor-negative, the baseline characteristics included an ECOG performance score of zero (65.3% versus 65.7%), brain metastases (8.5% versus 8.4%), visceral metastases (76.1% versus 71.3%), de novo status (50% versus 52.8%), recurrent status (50% versus 47.2%), and PIK3CA mutations not detected (68.2% versus 68%).

Regarding safety for hormone receptor-positive and hormone receptor-negative status, any treatment-emergent side effects occurred in 100% versus 99.4% in the Enhertu arm and 98.1% versus 100% in the THP arm; and side effects of grade 3 or higher occurred in 52.4% versus 57.7% in the Enhertu arm and 52.7% versus 52% in the THP arm; serious treatment-emergent side effects were noted in 28.2% versus 25.7% compared versus 29% versus 20.6%; treatment-emergent side effects leading to discontinuation occurred in 17% versus 25.1% and 27.1% versus 29.7%; and adjudicated drug-related ILD/pneumonitis occurred in 9.7% versus 14.9% and 0.5% versus 1.7%, respectively.

PIK3CA Mutation Status of the DESTINY-Breast09 Study

The median PFS for patients with PIK3CA mutations was 36.0 months versus 18.1 months in both arms, respectively. For those with PIK3CA not detected, the median PFS was 40.7 months for patients in the Enhertu plus Perjeta arm and 32.7 months in the THP arm.

The cORR for patients with PIK3CA mutations in the Enhertu plus Perjeta arm (116 patients) was 81% with 14.7% of patients having a CR and 66.4% having a PR versus a cORR of 73.6% in the THP arm (121 patients) with 4.1% having a CR and 69.4% having a PR. For those who did not have PIK3CA mutations detected, the cORR was 87.2% with 15.4% having a CR and 71.8% having a PR in the Enhertu plus Perjeta arm (266 patients) versus 80.8% with 10.5% having a CR and 70.3% having a PR in the THP arm (266 patients).

The median DOR for patients with PIK3CA mutations was 34.8 months in the Enhertu plus Perjeta arm versus 18.4 months in the THP arm. For those with PIK3CA mutations not detected, the median DOR was 39.2 months versus NC.

Baseline characteristics for patients with PIK3CA mutations between either arm included an ECOG performance status of zero (61.2% versus 62.8%), brain metastases (6.9% versus 5%), visceral metastases (64.7% versus 63.6%), recurrent disease status (53.4% versus 54.5%), and hormone receptor positive status (52.6% versus 52.9%). For those with PIK3CA mutations not detected, characteristics included an ECOG performance status of zero (69.5% versus 63.9%), brain metastases (6.4% versus 6%), visceral metastases (77.1% versus 71.8%), de novo disease (54.9% versus 54.5%), and hormone receptor positive status (54.9% versus 54.5%).

For those with PIK3CA status detected or not detected, any treatment-emergent side effects occurred in 100% versus 99.6% in the Enhertu arm and 99.2% versus 98.9% in the THP arm; grade 3 or higher treatment-emergent side effects occurred in 53% versus 55.8% and 45% versus 55.7%; treatment-emergent side effects leading to discontinuation in 17.4% versus 22.3% and 24.2% versus 30.2%; and adjudicated drug-related ILD/pneumonitis in 9.6% versus 13.2% and 2.5% versus 0.4%, respectively.

What was the DESTINY-Breast09 Study Design

Patients were randomly assigned one to one to one to either Enhertu plus placebo (blinded until the PFS analysis; 387 patients), Enhertu plus Perjeta (383 patients), or THP (387 patients). This analysis focused on the Enhertu plus Perjeta and THP arms.

The primary end point was PFS by blinded independent central review, with secondary end points including overall survival, PFS by investigator, objective response rate (ORR) by blinded independent central review/investigator, DOR, PFS-2 by investigator, and safety and tolerability.

The investigators noted that if patients discontinued Enhertu due to side effects except for higher than grade 2 interstitial lung disease, patients could switch to trastuzumab. For patients with hormone receptor-positive disease, concurrent use of endocrine therapy was allowed after six cycles of Enhertu or who discontinued Taxol.

Patients were enrolled if they had first-line HER2-positive advanced/metastatic breast cancer; a disease-free interval of six months or more from last neoadjuvant or adjuvant therapy; one prior line of endocrine therapy for advanced/metastatic breast cancer; and asymptomatic brain metastases were allowed.

“Enhertu (T-DXd) + Perjeta versus Taxol + trastuzumab + Perjeta (THP) for patients with HER2+ advanced/metastatic breast cancer: additional analyses of DESTINY-Breast9 in key subgroups of interest,” by Loibl S, Jiang Z, Barroso-Sousa R, et al Presented at the European Society for Medical Oncology Congress 2025, October 17–21, 2025; Berlin, Germany. LBA18.

Enhertu plus Perjeta demonstrated a significant progression-free survival (PFS) advantage over THP in HER2-positive advanced/metastatic breast cancer, regardless of prior treatment, hormone receptor status, or PIK3CA mutations. The study revealed higher objective response rates and longer duration of response for Enhertu plus Perjeta, with notable differences in safety profiles. Patients with hormone receptor-positive disease benefited from concurrent endocrine therapy. The study design included random assignment to treatment arms, with primary and secondary endpoints focusing on PFS, overall survival, and safety.

Enhertu plus Perjeta improved progression-free survival versus THP in patients with HER2-positive advanced or metastatic breast cancer across subgroups.


Enhertu Plus Perjeta Boosts Survival in HER2-Positive Breast Cancer

Adding Tecentriq to chemo resulted in survival outcomes comparable to placebo plus chemo in patients with advanced or recurrent endometrial cancer.

Adding Tecentriq to chemo resulted in survival outcomes comparable to placebo plus chemo in patients with advanced or recurrent endometrial cancer, according to results from the phase 3 AtTEnd/ENGOT-EN7 trial presented at the 2025 ESMO Congress.

Adding Tecentriq (atezolizumab) to chemotherapy resulted in survival outcomes comparable to placebo plus chemotherapy in patients with advanced or recurrent endometrial cancer, according to results from the phase 3 AtTEnd/ENGOT-EN7 trial presented at the 2025 ESMO Congress.

After a median follow-up of 48.9 months, overall survival (OS) did not significantly differ between patients treated with Tecentriq versus placebo, with a median of 36 months versus 30.5 months, respectively. The respective 12- and 24-month OS rates were 80.1% versus 73.8% and 61.1% versus 58.4%. Additionally, 12.1% of patients in the Tecentriq arm versus 29.2% in the placebo arm received subsequent immunotherapy.

In a planned subgroup analysis based on mismatch repair deficient (dMMR) status, patients with dMMR disease experienced significantly improved OS with Tecentriq. Median OS was not evaluable in the Tecentriq arm versus 31.8 months with placebo; 12- and 24-month rates were 86.8% versus 66.8% and 74.8% versus 54.8%. Subsequent immunotherapy was received by 7.4% versus 45.5% of patients in each respective arm.

Among patients with non-dMMR status, survival outcomes did not significantly differ. Median OS was 30 months with Tecentriq versus 30.2 months with placebo; 12- and 24-month rates were 77.8% versus 75.8% and 55.9% versus 58.8%. Subsequent immunotherapy was received by 13.8% versus 24.3% of patients, respectively.

Progression-free survival (PFS) outcomes numerically favored Tecentriq across all patients. Median PFS was 9.9 months versus 8.9 months, with 12- and 24-month rates of 44.7% versus 28.9% and 28.7% versus 16.8%. Among patients with dMMR disease, median PFS was not evaluable versus 6.9 months, with 12- and 24-month rates of 62.7% versus 23.3% and 52.1% versus 16.3%. In non-dMMR patients, median PFS was 9.5 months versus 9.2 months, with 12- and 24-month rates of 39.1% versus 30.2% and 21.7% versus 16.0%.

Overall survival (OS): The length of time patients are still alive after starting treatment.

Progression-free survival (PFS): The length of time patients live without cancer getting worse.

Mismatch repair deficient (dMMR): A genetic feature of some cancers where cells cannot fix DNA errors properly, making tumors more responsive to immunotherapy.

Objective response rate (ORR): The percentage of patients whose tumors shrink or disappear after treatment.

Complete response (CR): The disappearance of all signs of cancer.
Partial response (PR): A significant reduction in tumor size but not complete disappearance.

Duration of response (DOR): How long a patient’s tumor remains reduced or gone after treatment.

ECOG performance status: A scale (0-5) that measures a patient’s daily functioning and ability to care for themselves.


Objective response rate (ORR) and duration of response (DOR) in dMMR patients numerically favored Tecentriq. ORR was 82.4% with a complete response (CR) rate of 26.5% and a partial response (PR) rate of 55.9%, versus 75.7% with a CR rate of 18.9% and a PR rate of 56.8% with placebo. Median DOR was not evaluable versus 4.9 months, with 12- and 24-month rates of 66.9% versus 22.3% and 57.6% versus 14.8%. In non-dMMR patients, ORR was 75.6% versus 74.6%, with CR and PR rates of 15.1% and 60.5% versus 10.5% and 64.0%. Median DOR was 7.8 months versus 7 months, with 12- and 24-month rates of 35.1% versus 29.8% and 19.9% versus 15.0%.

“The addition of Tecentriq to chemotherapy did not demonstrate a statistically significant survival benefit in patients with advanced or recurrent endometrial carcinoma,” said Dr. Maria Pilar Barretina Ginesta. “In the pre-planned subgroup analysis based on mismatch repair status, substantial survival improvement was observed in patients with dMMR carcinomas.”

The study enrolled patients with advanced newly diagnosed or recurrent endometrial carcinoma or carcinosarcoma and randomly assigned them to receive paclitaxel and carboplatin area with Tecentriq or matching placebo. Following chemotherapy, patients received Tecentriq as maintenance or matching placebo.

Patients were stratified by country, histology, recurrent status, and dMMR status. Dual primary end points were PFS and OS.

Among all patients in the Tecentriq (360) and placebo (189) arms, 22.5% versus 23.3% had dMMR status. Recurrent disease status was 67.5% versus 66.7%, and 70.6% versus 68.2% had not received prior chemotherapy. In newly diagnosed disease, 75.2% versus 85.7% had measurable disease. Median age was 67 versus 65 years, and most patients were Caucasian (80.3% versus 75.7%), PD-L1–negative (68.6% versus 68.2%), and had intact ARID1A expression (68.9% versus 69.3%).

Any-grade side effects occurred in 98.6% versus 100%, with 75.8% versus 63.8% related to Tecentriq versus placebo. Grade 3 or higher side effects were observed in 26.4% versus 14.1%, with fatal side effects in 0.3% versus 0.5%. The most common side effects in the Tecentriq versus placebo arms were anemia (41.3% versus 35.1%), fatigue (39% versus 41.1%), neutropenia (40.7% versus 39.5%), peripheral sensory neuropathy (38.8% versus 39.5%), nausea (34% versus 37.3%), and hair loss (31.5% versus 36.2%).

"Final overall survival (OS) results from the randomized double-blind phase III AtTEnd/ENGOT-EN7 trial evaluating atezolizumab in combination with paclitaxel and carboplatin in women with advanced/recurrent endometrial cancer," by Dr. Maria Pilar Barretina Ginesta. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA39.

The phase 3 AtTEnd/ENGOT-EN7 trial evaluated the addition of Tecentriq (atezolizumab) to chemotherapy in patients with advanced or recurrent endometrial cancer. Results showed no significant overall survival (OS) benefit compared to placebo, except in patients with mismatch repair deficient (dMMR) disease, who experienced improved OS. Progression-free survival (PFS) outcomes favored Tecentriq across all patients. Objective response rate (ORR) and duration of response (DOR) were better in dMMR patients with Tecentriq. Side effects were common, with higher grade 3 or higher side effects in the Tecentriq arm.

Tecentriq Plus Chemo Shows Comparable Survival in Endometrial Cancer

In patients with extensive-stage small cell lung cancer Imdelltra plus chemoimmunotherapy was associated with positive outcomes.

Among patients with extensive-stage (ES) small cell lung cancer (SCLC), treatment with Imdelltra (tarlatamab) plus frontline chemotherapy and PD-L1 maintenance therapy was associated with positive safety and clinical outcomes, according to cohort results of the phase 1b DeLLphi-303 study presented during the European Society for Medical Oncology Congress 2025 and that were simultaneously published in 

At a median follow-up of 13.8 months, the objective response rate (ORR) was 71%, with a complete response rate of 5% and a partial response rate of 66%; 11% of patients had stable disease. Eight percent of patients had progressive disease, and 9% of patients’ responses were not evaluable (NE).

The median duration of response (DOR) was 11 months, the disease control rate was 82% and the median duration of disease control was 10.7 months. Additionally, disease control was sustained for at least 52 weeks in 39% of patients, with ongoing responses in 49% of patients at data cutoff with data continuing to mature, said lead study author Dr. Martin Wermke, director of Trial Management/Early Clinical Trial Unit, NCT/UCC Early Clinical Trial Unit, of the German Cancer Research Center, University Hospital Carl Gustav Carus Dresden in Dresden, Germany.

Objective response rate (ORR): the percentage of patients in a clinical study whose cancer significantly shrinks or completely disappears after receiving a specific treatment.

Duration of response (DOR): the length of time that a patient's cancer remains controlled (either shrinking or gone) without the disease progressing.

Disease control rate (DCR): the percentage of patients whose cancer either shrinks, disappears or stays stable (does not grow significantly) for a period of time after treatment.

Cytokine release syndrome (CRS): a side effect of some immunotherapies that involves a rapid, large release of immune substances (cytokines) into the blood, causing symptoms like fever, fatigue and sometimes more serious problems.

Immune effector cell-associated neurotoxicity syndrome (ICANS): a possible side effect of certain immune-based cancer treatments that causes symptoms related to inflammation of the brain or nervous system, such as confusion, difficulty speaking or seizures.

ECOG performance status: a simple scale (from 0 to 4) used by doctors to measure and track a cancer patient's overall well-being and ability to perform everyday activities.

Regarding safety, with a median duration of treatment of 46 weeks, three dose-limiting toxicities were observed overall, with all patients experiencing treatment-related side effects that were grade 3 (severe, 43%) or 4 (life-threatening, 35%), with one patient who died from a treatment-related side effect due to sepsis, attributable to the chemotherapy component of the regimen, Wermke said.

Imdelltra-related side effects that led to treatment discontinuations occurred in 6% of patients, and immune-related adverse events — not including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurological events — were reported in 2% of patients.

The addition of Imdelltra to chemoimmunotherapy demonstrated a manageable safety profile that was consistent with the profiles of each individual agent, explained Wermke.

“I hope I could convince you that the combination of another frontline chemoimmunotherapy [that is] PD-L1 targeting in the maintenance [setting] is safe and has a manageable toxicity profile,” Wermke said in an oral presentation of the data. “There is no indication of additive or synergistic toxicity.”

Currently, standard treatment for patients with ES-SCLC comprises chemoimmunotherapy followed by PD-1/PD-L1 treatment as maintenance. Imdelltra is a bispecific T-cell engager that has been assessed in the second-line setting as a single agent in the phase 3 DeLLphi-304 trial and in the frontline maintenance setting with a PD-L1 inhibitor in this patient population, as seen in parts 5, 6 and 8 of the phase 1b DeLLphi-303 study.

At the 2025 ESMO Congress, Wermke presented on safety and efficacy outcomes from parts 2, 4 and 7 from the phase 1b DeLLphi-303 study, which explored Imdelltra in combination with frontline chemoimmunotherapy, followed by Imdelltra with PD-L1 maintenance therapy in patients with ES-SCLC.

The study enrolled adult patients with ES-SCLC who had received one cycle of chemoimmunotherapy, consisting of platinum-etoposide plus an anti-PD-L1 inhibitor, regardless of response to therapy. Patients were also required to have measurable disease, an ECOG performance status of 0 or 1, and no active autoimmune disease or disease that required immunosuppressive therapy. Those with treated and asymptomatic brain metastases were permitted.q

In cycles 1 to 3, patients received Imdelltra at 20 mg intravenously (IV) every three weeks plus platinum-etoposide (carboplatin to match area under the curve 5 IV on day 1 and etoposide at 100 mg/m

 on days 1 to 3) and a PD-L1 inhibitor, which consisted of Tecentriq (atezolizumab) at 1200 mg IV every 3 weeks or Imfinzi (durvalumab) at 1500 mg IV every three weeks. In the frontline maintenance setting, which was cycles 4 and beyond, patients received Imdelltra at 20 mg IV every three weeks plus either of the PD-L1 inhibitors at the aforementioned doses. Treatment was administered until disease progression.

The coprimary end points were dose-limiting toxicities, treatment-emergent side effects and treatment-related side effects; secondary end points were ORR, DOR, disease control, progression-free survival (PFS), and overall survival (OS).

Regarding baseline characteristics, the median age across both arms was 63 years, and 67% of patients were male. Patients were mostly White (74%), followed by Asian (16%), Other (9%) and Black (1%). At diagnosis, 77% had ES disease and 55% had an ECOG performance status of 1. Three-fourths of patients were former smokers, and 67% had prior receipt of a PD-L1 inhibitor in the first standard-of-care cycle; 16% and 45% of patients had treated asymptomatic brain metastases and liver metastases, respectively. The median sum of diameters of target lesions was 82.3 mm.

Wermke noted that the trial was not designed to compare the PD-L1 inhibitors and there were no randomizations between the treatment arms, adding that there were imbalances in baseline characteristics between the Tecentriq and Imfinzi groups.

Further efficacy data showed that the median PFS was 10.3 months starting from the first dose of Imdelltra treatment; the Kaplan-Meier estimate of the 12-month PFS rate was 43.1%. The median OS is not yet estimable; however, the Kaplan-Meier estimate of the 12-month OS rate with the Imdelltra regimen was 80.6%.

Investigators also assessed treatment-emergent CRS and ICANS by cycle, which primarily occurred during cycle 1 of Imdelltra (59%) and were mostly of grades 1 (mild)/2 (moderate); all CRS/ICANS events resolved. CRS and ICANS events led to both dose interruptions and discontinuations in 1% of patients each, with no fatalities reported. The median time to CRS onset from the last prior Imdelltra dose was 13.3 hours, and the median time to ICANS onset from the same time point was five days.

Wermke concluded that these data support further investigation of this regimen, which will be explored in the phase 3 DeLLphi-312 study.

“Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study,” Dr. Martin Wermke et al., 

The combination of Imdelltra (tarlatamab) with frontline chemotherapy and PD-L1 maintenance therapy in extensive-stage small cell lung cancer (ES-SCLC) patients showed promising safety and efficacy results in the phase 1b DeLLphi-303 study. With a median follow-up of 13.8 months, the objective response rate was 71%, and the disease control rate was 82%. The safety profile was manageable, with severe treatment-related side effects in 43% of patients. The study supports further investigation of this regimen in the phase 3 DeLLphi-312 study.

Ariana Pelosci

Hernexeos Effective in HER2-Mutated NSCLC

Enhertu Plus Perjeta Boosts Survival in HER2-Positive Breast Cancer

Tecentriq Plus Chemo Shows Comparable Survival in Endometrial Cancer

Imdelltra Plus Chemoimmunotherapy Safely Elicits Responses in ES-SCLC

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