Amgen Unveils New Data for Imdelltra in Small Cell Lung Cancer at WCLC 2024
Amgen presented promising new results for Imdelltra, a first-in-class immunotherapy, at the 2024 World Conference on Lung Cancer (WCLC). These findings came from two key studies:
DeLLphi-303, exploring the use of Imdelltra with a PD-L1 inhibitor as a first-line maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC)
DeLLphi-301, which provided long-term data on its safety and effectiveness
DeLLphi-303 Phase 1b Study: First-Line Maintenance Therapy
Data from the DeLLphi-303 Phase 1b study highlighted Imdelltra combined with a PD-L1 inhibitor as a first-line maintenance therapy for ES-SCLC, showing promising safety and sustained disease control. Key highlights include:
Imdelltra plus PD-L1 inhibitor: Showed a favorable benefit-risk ratio without any new or unexpected safety issues.
Imdelltra plus durvalumab: Achieved a disease control rate (DCR) of 62.5%, with the median duration of disease control (DoDC) not yet estimable.
Imdelltra plus atezolizumab: Recorded a DCR of 62.5% and a median DoDC of 7.2 months.
Patients in the trial started maintenance treatment around 3.5 months after initial chemoimmunotherapy. In terms of survival outcomes:
Imdelltra plus durvalumab: Showed a 9-month overall survival (OS) of 91.8% and a median progression-free survival (PFS) of 5.3 months.
Imdelltra plus atezolizumab: Achieved a 9-month OS of 86.7% and a median PFS of 5.6 months.
Treatment-related adverse events (TRAEs) were reported in both arms, with dose interruptions occurring in 15% of patients treated with Imdelltra plus durvalumab and 17% of those treated with IMDELLTRA plus atezolizumab.
DeLLphi-301 Phase 2 Study: Extended Follow-up Data
The Phase 2 DeLLphi-301 study offered extended data on Imdelltra's long-term performance in patients with ES-SCLC who had already undergone platinum-based chemotherapy. Out of 100 patients receiving 10 mg of Imdelltra every two weeks, the results included:
An objective response rate (ORR) of 40%, with half of the responders maintaining their response at the data cutoff.
Stable disease in 30% of patients, with a median disease control duration of 6.9 months (95% CI: 5.4-8.6).
A median OS of 15.2 months, with comparable outcomes regardless of progression-free interval after first-line chemotherapy.
These findings underscore IMDELLTRA’s sustained effectiveness and favorable safety profile, supporting its continued use in patients with ES-SCLC.
About Imdelltra (tarlatamab)
Imdelltra, approved by the U.S. FDA in May 2024, is a novel immunotherapy developed by Amgen. It works by targeting DLL3 on cancer cells and CD3 on T cells, facilitating the destruction of cancer cells by T cells. Since DLL3 is expressed in up to 96% of SCLC cases but minimally present on healthy cells, it presents an exciting therapeutic target.
Datopotamab Deruxtecan Demonstrates Median Overall Survival of 14.6 Months in Patients with
Advanced Nonsquamous NSCLC in TROPION-Lung01 Phase III Trial
The Phase III TROPION-Lung01 trial, which evaluated AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd) against chemotherapy, has shown encouraging overall survival (OS) results in patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). These findings indicate a meaningful improvement in OS for patients treated with datopotamab deruxtecan compared to the chemotherapy drug docetaxel, the current standard of care for this cancer type. This study focused on patients who had already undergone at least one line of prior treatment.
Datopotamab deruxtecan is a TROP2-targeting antibody-drug conjugate (ADC), developed through collaboration between AstraZeneca and Daiichi Sankyo, which was designed to treat cancers expressing the TROP2 protein.
Results Overview
In the general population studied in the trial, OS favored datopotamab deruxtecan over docetaxel, with a median survival of 12.9 months versus 11.8 months, although this difference did not reach statistical significance. However, in the key subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan demonstrated a 2.3-month improvement in OS compared to docetaxel (14.6 months versus 12.3 months). This survival benefit was consistent regardless of whether the patients had tumors with specific genomic alterations.
Conversely, for patients with squamous NSCLC, the treatment did not show an OS improvement, consistent with earlier analyses.
Study Design and Population
The TROPION-Lung01 trial enrolled patients with NSCLC, and the distribution of tumor histology between the treatment groups was representative of real-world patterns, with approximately 75% of patients having nonsquamous NSCLC. Additionally, about 17% of participants had tumors with actionable genomic alterations, including epidermal growth factor receptor (EGFR) mutations, a common target in cancer therapy.
These overall survival results build on earlier positive outcomes from the trial regarding progression-free survival (PFS). At the 2023 European Society for Medical Oncology Congress, data revealed that datopotamab deruxtecan significantly improved PFS compared to chemotherapy in the overall patient population. The drug showed a particularly strong PFS benefit in patients with nonsquamous NSCLC, reinforcing its potential in this subgroup.
Regulatory Implications
The OS data from TROPION-Lung01 has been shared with regulatory authorities as they review applications for the use of datopotamab deruxtecan in this specific indication. The results from both the PFS and OS analyses indicate that this drug could offer a valuable alternative for patients with advanced nonsquamous NSCLC who have limited treatment options after progressing on prior therapies.
Libtayo (cemiplimab) Shows Sustained Survival Benefits After Five Years in Advanced NSCLC Patients
New data presented at the World Conference on Lung Cancer (WCLC) reveal that Libtayo monotherapy nearly doubled median overall survival (OS) and significantly reduced both the risk of death and disease progression by 41% and 50%, respectively, compared to standard chemotherapy.
Additionally, results reviewed at the WCLC included findings on OS, progression-free survival (PFS), and response rates among patients who received chemotherapy alongside Libtayo after their cancer progressed.
Five-Year Results of EMPOWER-Lung 1 Trial
Regeneron Pharmaceuticals announced the final five-year data from the Phase 3 EMPOWER-Lung 1 trial, which investigated Libtayo as a first-line treatment for advanced non-small cell lung cancer (NSCLC) in adults. The study focused on patients whose tumors expressed at least 50% PD-L1 and lacked EGFR, ALK, or ROS1 mutations. The trial's results confirmed that Libtayo continued to outperform chemotherapy in this patient population, demonstrating durable survival benefits in line with earlier analyses conducted at the one-year mark.
1-year | 1-year | 5-years | 5-years | |
Libtayo | Chemotherapy | Libtayo | Chemotherapy | |
Overall survival | Not reached | 14months | 26 months | 13months |
Progression-free survival | 8 months | 6 months | 8 months | 5 months |
Objective Response Rate | 39% | 20% | 46.5% | 21% |
The EMPOWER-Lung 1 trial allowed patients whose disease progressed while on Libtayo to switch treatments, with some patients (n=75) adding four cycles of chemotherapy. In these cases, the combination led to a median OS of 15 months, a median PFS of 7 months, and an objective response rate (ORR) of 28%.
PD-L1 Expression and Survival Correlation
An exploratory analysis within the trial revealed a direct link between the level of PD-L1 expression and survival outcomes for patients treated with Libtayo. Those whose tumors had PD-L1 expression levels of 90% or more (n=99) experienced the most substantial benefits, achieving a median OS of 39 months and a median PFS of 15 months. Interestingly, this relationship between PD-L1 expression and outcomes was not observed in patients receiving chemotherapy alone.
Safety Profile After Five Years
No new safety concerns were noted after five years in the trial, which included 356 patients treated with Libtayo and 343 patients treated with chemotherapy.
Boehringer’s Zongertinib Shows Promising Efficacy and Tolerability in Treated HER2-Mutated Lung Cancer Patients
Boehringer Ingelheim's Zongertinib shown encouraging results in patients with HER2-mutated lung cancer, as revealed by the Beamion LUNG-1 Phase Ib trial.
The trial achieved its primary goal, showing a notable objective response rate (ORR) of 66.7%, according to a blinded independent review. The therapy also showed preliminary effectiveness in patients with brain metastases, with an intracranial response rate of 33% and a disease control rate (DCR) of 74%.
Additionally, the treatment was well tolerated, with manageable side effects and a low discontinuation rate of 3%. As two-thirds of the patients remain on treatment, more mature data, including progression-free survival (PFS) and duration of response (DoR), will be shared later this year.
Positive Outcomes from Phase Ib Cohort of Beamion LUNG-1 Trial
Boehringer Ingelheim recently shared favorable findings from a Phase Ib primary analysis of Cohort 1 from the Beamion LUNG-1 trial. This trial evaluated zongertinib (BI 1810631) in pre-treated patients with advanced non-small cell lung cancer (NSCLC) carrying HER2 mutations. Zongertinib displayed significant objective response and tolerability in this patient group.
As of May 2024, 132 patients had been treated with either 120 mg or 240 mg of zongertinib daily (75 patients at 120 mg and 57 at 240 mg). In Cohort 1 (120 mg), a confirmed ORR of 66.7% was observed, with a 97.5% confidence interval and statistical significance, as assessed by the independent review.
Across both dose groups, tumor shrinkage of any size was noted in 94% of patients, based on investigator evaluations. The study was designed to explore different doses of zongertinib, with patients initially randomized 1:1 to receive either 120 mg or 240 mg.
Following an interim analysis, the 120 mg dose was selected for further investigation, and 17 more patients were enrolled. In the randomized portion of the trial, the 120 mg group had a 72.4% response rate, while the 240 mg group showed a 78.2% response rate, with DCRs of 95% and 100%, respectively.
Zongertinib Shows Brain Activity and Manageable Side Effects
The data from Phase Ib, Cohort 1 also suggested that zongertinib might have preliminary brain activity. Among patients with asymptomatic brain metastases, 33% (120 mg group) and 40% (240 mg group) demonstrated confirmed objective responses, with disease control rates of 74% and 92%, respectively, based on RANO-BM criteria. Brain metastases are a frequent complication in NSCLC and significantly worsen outcomes and quality of life. Up to 30% of NSCLC patients with HER2 mutations present with brain metastases at the time of diagnosis.
Zongertinib, a HER2-specific tyrosine kinase inhibitor (TKI), is an experimental oral drug developed to treat patients with advanced NSCLC who have HER2 mutations. It was designed to target HER2 without affecting wild-type EGFR, minimizing associated side effects. The Beamion LUNG-2 Phase III trial is currently enrolling participants to evaluate zongertinib as a first-line treatment compared to standard therapies in patients with HER2-mutated NSCLC.
Zongertinib Shows Low Toxicity and Manageable Adverse Events
Zongertinib showed favorable tolerability across both dose groups (120 mg and 240 mg), with no treatment-related deaths. A low percentage of patients experienced adverse events that led to dose reductions (11%) or treatment discontinuation (3%). No new safety concerns, including treatment-related interstitial lung disease (ILD), were identified. Serious treatment-related side effects (Grade 3 or higher) occurred in 17% of patients in the 120 mg group and 19% in the 240 mg group. The most common side effects were mild to moderate, including diarrhea (43% in the 120 mg group, 11% in the 240 mg group) and rash (19% and 8%, respectively).
About Zongertinib
Zongertinib (also called BI 1810631) is an investigational HER2-targeted oral tyrosine kinase inhibitor designed for the treatment of HER2-mutated NSCLC. The U.S. FDA granted Fast Track designation for zongertinib in 2023, followed by Breakthrough Therapy designation from both the U.S. FDA and China's CDE in 2024 for treating adults with advanced NSCLC who have HER2 mutations and have undergone prior systemic therapy. HER2 belongs to the ErbB family of receptor tyrosine kinases, which play a key role in cellular signaling. Preclinical studies suggest that zongertinib may hold potential for treating other HER2-driven solid tumors, either as a stand-alone therapy or in combination with antibody-drug conjugates (ADCs) or KRAS inhibitors.
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