Lung cancer Highlights: ASCO 2021

DelveInsight’s consultants have extracted some of the pivotal abstracts that highlighted innovations and breakthroughs in the Lung cancer domain. Read the analysis below.

Abstract #9007: Patritumab deruxtecan (HER3-DXd) demonstrated preliminary evidence of clinically meaningful and durable tumor response in advanced EGFRm NSCLC patients

Daiichi Sankyo presented the promising clinical data of patritumab deruxtecan from the extended follow-up phase 1 study in patients with locally advanced or metastatic TKI-resistant, EGFR-mutated NSCLC. HER3 is expressed in >80% of EGFR-mutant NSCLC, and overexpression is associated with poor outcomes. Patritumab deruxtecan is a novel HER3-directed antibody-drug conjugate (ADC) that consists of the monoclonal antibody patritumab, a tetrapeptide-based linker, and a topoisomerase I inhibitor payload. In 44 patients who had previously received osimertinib (Tagrisso) and platinum-based chemotherapy (PBC), the benefit derived from the ADC proved to be similar, with a confirmed objective response rate (ORR) of 39%, a disease control rate (DCR) of 68%, and a median progression-free survival (PFS) of 8.2 months. 

Data from this study validated the design of the recently initiated pivotal HERTHENA-Lung01 trial in a similar patient population. The agent is currently under investigation in NSCLC, metastatic breast cancer, and colorectal cancer.

Expert Views "HER3 represents a novel target for therapeutic development as it is broadly expressed in NSCLC. These results are encouraging since the safety profile was consistent with previous findings and response to patritumab deruxtecan was seen irrespective of the level of HER3 expression or mechanism of resistance to prior therapies."

Abstract #9003: First-ever KRAS G12C inhibitor showed a clinical significant overall survival benefit in phase 2 CodeBreaK100 trial

Amgen presented the data on overall survival, a secondary endpoint, from the Phase 2 results of the CodeBreaK 100 clinical study for LUMAKRASTM (sotorasib) in previously treated patients with NSCLC at ASCO 2021. Sotorasib, which is the first KRAS G12C inhibitor, has recently got the U.S. FDA approval in for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. Sotorasib showed a median overall survival (OS) of 12.5 months among 124 evaluable patients, the majority of which were previously treated with both platinum-based chemotherapy and immunotherapy (81%). The results confirmed an objective response rate (ORR) of 37.1%, duration of response (DoR) of 11.1 months and disease control rate (DCR) of 80.6%. 

Recently, the FDA has also approved the Guardant360 CDx assay as a companion diagnostic for tumor mutation profiling to identify patients with locally advanced or metastatic NSCLC whose tumors harbor the KRAS G12C mutation and may derive benefit from sotorasib.

Expert Views: "Sotorasib is the first KRAS G12C inhibitor to show an overall survival benefit, and the data represent a major step forward for patients with KRAS G12C-mutated NSCLC where the standard of care options are suboptimal".

Abstract #9046: Favorable Overall Response Rate (ORR) with encouraging median Progression-free survival (PFS) of 8.2 months, with a minimum duration of response (DoR) of more than 6 months

At ASCO 2021, Immutep reported interim positive data from its Phase II study (TACTI-002; NCT03625323), investigating eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic non-small cell lung carcinoma. At the data cutoff date of Apr 16 2021, sustained and durable responses were observed. In this trial, an ORR of 41.7% (n=15) is achieved in patients with an intention-to-treat basis and 48.4% in evaluable patients. In this study, it was observed that 58% of responses were maintained beyond six-month. According to a local investigator read, the median PFS in patients with PD-L1 unselected expression is 8.2 months. This is quite encouraging for a chemotherapy-free first-line treatment. The median PFS in the 50% PD-L1 subgroup is 11.8 months, while the median PFS in the 1% PD-L1 category is 4.1 months. It can be said that, when compared to studies where Pembrolizumab has been administered as monotherapy in comparable patient groups, the mPFS of 8.2 months is encouraging.

Abstract #9020: New Overall Survival (OS) and updated overall response data backing up Tabrecta as a foundation of targeted therapy for METex14 NSCLC patients

Last year, Tabrecta (capmatinib) was approved as the first FDA-approved therapy to treat NSCLC with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping). At ASCO 2021, Novartis/Incyte announced the first published overall survival and updated overall response data of GEOMETRY Mono-1 Study in patients in both treatment-naïve and previously-treated patients with METex14 metastatic NSCLC. In this study, the efficacy analysis included patients with METex14 NSCLC who were treatment-naive (Cohort 5b and 7) and those who had previously received first-line or second-line therapy (expansion Cohort 6 and Cohort 4) for their advanced disease (data cutoff: Sep 18, 2020). In the first published mature data, Tabrecta showed a median OS of 20.8 months in treatment-naive patients (Cohort 5b) and 13.6 months in previously-treated patients (Cohort 4). Median OS for Cohorts 6 and 7 and Duration of response (DoR) for Cohort 7 are not yet reached at the time of data cutoff. mDoR based on BIRC assessment was 12.6 months among treatment-naïve patients (Cohort 5b; and Cohort 7; patients, respectively), and 9.7 months and 8.4 months among previously-treated patients (Cohort 4; and Cohort 6; patients, respectively). ORR of 67.9% and 65.6% among treatment-naïve patients (Cohort 5b; and Cohort 7; respectively), and 40.6% and 51.6% among previously-treated patients (Cohort 4 (2/3L); and Cohort 6 (2L); respectively). No new safety signals or unexpected safety findings were observed.

Abstract #8512: Encouraging Overall Response Rate (ORR) with low grade 3 toxicity/ pneumonitis demonstrated in the KEYNOTE-799 trial 

Merck presented findings from the KEYNOTE-799 trial of Pembrolizumab plus Platinum Chemotherapy and Radiotherapy for Unresectable, Locally Advanced, Stage III NSCLC.,at ASCO 2021. The current standard of care in this setting is chemoradiation followed by a "consolidation regimen" of AstraZeneca's ImfinziPneumonitis is the most major safety concern here. The preliminary findings were encouraging with the ORR in cohorts A and B of ~70%, regardless of PD-L1 status, and low grade 3 toxicity/ pneumonitis in both arms (8.0% vs. 6.9% in Cohort A and B, respectively). Furthermore, patients' progression-free survival (PFS) and overall survival rates were also encouraging. The overall survival rate in Cohort A and B were 81.3% vs. 87% (at 12 months). In addition, at 12 months, PFS was ~70% in both cohorts. In patients with previously untreated, locally advanced, stage III NSCLC, regardless of PD-L1 TPS or tumor histology, Pembrolizumab with Platinum Chemotherapy and Radiotherapy demonstrated promising antitumor efficacy and acceptable safety.

DelveInsight recently published an in-depth analysis of the Lung Cancer market covering several indications, including the Non-Small Cell Lung Cancer and Small Cell Lung Cancer market. Get in touch with us to discuss more at info@delveinsight.com.