Janssen presented promising follow-up data from the CHRYSALIS-2 study. This phase 1b/2 trial explored the safety and efficacy of combining Rybrevant (amivantamab) and lazertinib with platinum-based chemotherapy for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) and were previously treated with EGFR TKIs.
In this cohort of 20 patients, the treatment achieved a 50 per cent objective response rate, with 11 patients continuing treatment. Median progression-free survival was 14 months, and many responders maintained a response for at least six months. Some common adverse events included neutropenia, rash, and infusion-related reactions.
The trial outcomes show the potential of this combination therapy for previously treated EGFR-mutated advanced NSCLC, highlighting ongoing efforts to improve treatment options for these patients.
Gilead Sciences has unveiled promising initial findings from its Phase 2 EVOKE-02 study, which examines the potential of Trodelvy (sacituzumab govitecan) in combination with Merck's anti-PD-1 therapy Keytruda (pembrolizumab), with or without platinum agents. This research focuses on patients who have not previously received treatment for advanced or metastatic non-small cell lung cancer (NSCLC) and lack actionable genomic alterations.
The preliminary analysis of the EVOKE-02 study includes results from two distinct cohorts: one with Trodelvy in combination with Keytruda for first-line advanced or metastatic squamous/non-squamous NSCLC patients with a PD-L1 tumour proportion score (TPS) of ≥ 50% (Cohort A) and another for patients with TPS < 50% (Cohort B). In Cohort A (n=29), the confirmed and unconfirmed objective response rate (ORR) was an impressive 69%, with a disease control rate (DCR) of 86%. Cohort B (n=32) displayed a confirmed and unconfirmed ORR of 44% and a DCR of 78%. When considering both cohorts together, the ORR was 56%, and the DCR was 82%. The median duration of response (DoR) was not concluded at the time of data collection, with a DoR rate of 88% at six months observed in both cohorts.
The safety profile of the combination of Trodelvy and Keytruda in the EVOKE-02 study was in line with the known safety profiles of each drug.
Gilead initiated two clinical trial collaborations and supply agreements with Merck in January 2022. These agreements aimed to assess the combination of Trodelvy and Merck's Keytruda in the Phase 2 EVOKE-02 signal-seeking study and the ongoing Phase 3 EVOKE-03 study for first-line NSCLC.
Bristol Myers Squibb released six-year outcomes from Part 1 of the Phase 3 CheckMate -227 trial, showcasing the enduring and long-term survival benefits of Opdivo (nivolumab) and Yervoy (ipilimumab) compared to traditional chemotherapy in the initial treatment of patients dealing with metastatic non-small cell lung cancer (mNSCLC). These benefits are consistent regardless of the levels of PD-L1 expression.
With a minimum follow-up duration of over six years (73.5 months), the longest for any Phase 3 trial using immunotherapy in mNSCLC, the key findings are as follows:
PD-L1 Expression ≥1%: Among patients with tumour PD-L1 expression of ≥1%, the six-year survival rate for those treated with Opdivo plus Yervoy was 22%, while it was 13% for those receiving chemotherapy.
PD-L1 Expression <1% (Exploratory Analysis): In an exploratory analysis of patients with PD-L1 expression <1%, more than three times as many patients treated with Opdivo plus Yervoy were alive at six years compared to those treated with chemotherapy (16% vs. 5%).
Tumour Burden Reduction: For patients who responded to treatment, a more significant proportion experienced a tumour burden reduction of ≥80% with Opdivo plus Yervoy compared to chemotherapy, in both the PD-L1 ≥1% (15% vs. 3%, respectively) and <1% (8% vs. 1%, respectively) subgroups. The six-year overall survival (OS) rates for patients with a tumour burden reduction of ≥80% with Opdivo plus Yervoy were higher compared to chemotherapy (59% vs. 42% for PD-L1 ≥1% and 77% vs. 0% for PD-L1 <1%, respectively).
Enhertu, a collaborative effort between AstraZeneca and Daiichi Sankyo, continues to exhibit robust and enduring tumour responses in patients previously receiving treatment for HER2-mutant advanced lung cancer. The encouraging findings stem from the Phase II DESTINY-Lung02 trial.
In this primary analysis, the objective response rates (ORR) were notable, with 49% in the 5.4mg/kg dosage group and an even more impressive 56% in the 6.4mg/kg dosage group. Notably, the safety profile observed for both dosage levels aligns with Enhertu's overall safety record, with the 5.4mg/kg dose demonstrating a particularly favourable safety profile within this patient cohort.
Additional secondary endpoint data further underscore the efficacy of Enhertu in this setting. Progression-free survival (PFS) reached a median of 9.9 months at the 5.4mg/kg dose and a remarkable 15.4 months at the 6.4mg/kg dose, as assessed by BICR. Notably, regarding overall survival (OS), patients in the 5.4mg/kg group achieved a median OS of 19.5 months, while the 6.4mg/kg group had not reached a median OS at the time of analysis.
The FLAURA2 Phase III trial has unveiled promising findings regarding the treatment of locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). The combination of Tagrisso (osimertinib) with chemotherapy has demonstrated a substantial and clinically significant enhancement in progression-free survival (PFS) when contrasted with Tagrisso monotherapy, which is currently established as the standard of care for initial treatment.
The combination of Tagrisso plus chemotherapy has proven highly effective, reducing the risk of disease progression or death by a substantial 38% compared to Tagrisso alone. According to investigator assessments, the combination therapy extended the median PFS by an impressive 8.8 months compared to Tagrisso monotherapy. Furthermore, when evaluated by a blinded independent central review (BICR), the combination therapy demonstrated consistent results, extending the median PFS by 9.5 months. Importantly, this clinically meaningful PFS benefit was observed across all predefined subgroups, including factors such as sex, race, type of EGFR mutation, age at diagnosis, smoking history, and central nervous system (CNS) metastases at baseline.
While the analysis has yet to provide mature data on overall survival (OS), a favourable trend has been noticed in the Tagrisso plus chemotherapy group.