Role of Antibody-Drug Conjugates in NSCLC Treatment: Insights from EVOKE-02 

Briefly discuss the potential role of ADCs in NSCLC with non-actionable mutations.

What is the rationale for use of ADCs in this treatment space?

What characteristics may allow ADCs to be more advantageous in this treatment space over other traditional chemotherapy and targeted agents?

Which ADCs are most likely to have potential benefit here and why?

Please review the rationale and study design for EVOKE-02 and discuss key efficacy and safety data and the implications these findings may have on the treatment landscape. (

Cappuzzo et al. WLC 2024. Efficacy results by histology from the EVOKE-2 study

ASCO 2024 Patel et al. SG + Pembro in 1L mNSCLC with PD-L1 ≥50%: Cohort A of EVOKE-02)

What do data demonstrateregarding the efficacy of SG + pembro in patients with NSCLC and how does response differ by PD-L1 expression?

Other key takeaways? What implications could these findings have on clinical practice?

Which patients stand to benefit the greatest from this treatment approach?

Videos

Benjamin Levy, MD, leads discussion on the promising potential of antibody-drug conjugates (ADCs) in treating non-small cell lung cancer (NSCLC) with non-actionable mutations, while Helena A. Yu, MD, presents an overview of the EVOKE-02 study, emphasizing key efficacy and safety data that could significantly impact the current treatment landscape. 

Treatment Strategies for NSCLC with Non-Actionable Mutations 

Please provide a brief overview of the landscape surrounding first-line treatment of NSCLC.

How do treatment approaches differ between patients with actionable vs non-actionable mutations?

Briefly outline your general treatment approach for NSCLC with non-actionable mutations. (

What is the role of immunotherapy (IO) in this treatment space?

What factors are most critical for guiding treatment selection?

How may your treatment approach differ based on PD-L1 TPS status?

Mark Socinski, MD; Helena A. Yu, MD; Zosia Piotrowska, MD, MHS; Julia Rotow, MD; and Benjamin Levy, MD, provide a concise overview of current first-line treatment options for non-small cell lung cancer (NSCLC), including their approaches for NSCLC with non-actionable mutations and the influence of PD-L1 tumor proportion score status on treatment choices. 

Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01

-activating mutations occur in 14% to 38% of patients with NSCLC

Salvage therapies after EGFR TKI therapy and platinum-based chemotherapy provide only limited and transient clinical benefit

CNS metastases are common in this population, and therapies to ensure CNS control are needed

A phase 1 study of HER3-DXd for advanced NSCLC demonstrated efficacy in patients with 

-activating mutations and diverse mechanisms of resistance to EGFR TKIs

Promising data from the phase 1 trial led to initiation of the phase 2 HERTHENA-Lung01 trial of HER3-DXd in patients with 

-mutated NSCLC who were treated previously with EGFR TKI and platinum-based chemotherapy

Progression on most recent systemic therapy

Prior EGFR TKI and prior platinum-based chemotherapy

Inactive or previously treated asymptomatic brain metastases allowed

R1:1 to fixed dose HER3-DXd IV Q3W or HER3-DXd uptitration

Clinically meaningful efficacy was observed in the overall population and across subgroups

The safety profile of HER3-DXd was manageable and tolerable and consistent with previous reports

HER3-DXd emerged as a promising therapy for patients with 

-mutated NSCLC after the failure of EGFR TKI and platinum-based chemotherapy, for whom available treatment options provide only limited efficacy

Expert oncologist Helena Yu, MD, reviews data from HERTHENA-Lung01 following the IASLC 2023 World Conference on Lung Cancer and considers how patritumab deruxtecan will fit into clinical practice.  

Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01 

Helena A. Yu, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses findings from a phase 1 trial (NCT05194982) investigating the bispecific antibody-drug conjugate (ADC) BL-B01D1, which is directed against both HER3 and EGFR, in patients with locally advanced or metastatic solid tumors such as non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), nasopharyngeal carcinoma, and head and neck squamous cell carcinoma.

Dr Yu on the Efficacy of BL-B01D1 in Advanced Solid Tumors

The findings from this trial, presented at the 2023 ASCO Annual Meeting at a median follow-up of 4.1 months, included data from 195 patients with at least 1 tumor assessment, 45.3% of whom responded to treatment with BL-B01D1. These are promising early findings from a phase 1 dose-escalation study, Yu says. When overall response rate (ORR) was stratified by tumor type, the ADC generated the highest ORR, 63.2%, in patients with 

-mutant NSCLC. This finding was expected based on the prevalence of both EGFR and HER3 in NSCLC, Yu notes.

The patients with NSCLC who were enrolled in the trial were divided into 2 groups: those with 

-mutant NSCLC had received prior EGFR TKIs, most of which were third-generation EGFR TKIs such as osimertinib (Tagrisso), and 74% of these patients had received prior platinum-based chemotherapy. Given the heavily pretreated nature of the 

-mutant NSCLC population, the 63.2% ORR in the third-line setting and beyond was notable, according to Yu.

 wild-type NSCLC have limited treatment options after first-line chemoimmunotherapy and no targeted therapies, Yu explains. In this population, BL-B01D1 elicited an ORR of 44.9%, which supports the further investigation of ADCs in patients with NSCLC without driver mutations, Yu emphasizes.

This trial enrolled a small SCLC cohort consisting of 7 patients, of whom 1 achieved a partial response. The small size of the SCLC cohort in this phase 1 trial demonstrates the importance of further research in this population, Yu concludes.

Helena A. Yu, MD, discusses findings from a phase 1 trial investigating the bispecific antibody-drug conjugate BL-B01D1, which is directed against both HER3 and EGFR, in patients with locally advanced or metastatic solid tumors such as non–small cell lung cancer and small cell lung cancer.

Dr Yu on the Investigation of BL-B01D1 in Lung Cancer

Helena A. Yu, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses treatments for 

The FLAURA study, which read out in late 2017, showed that osimertinib (Tagrisso) had a doubling of median progression-free survival (PFS) compared with what was previously the standard of care for these patients. Osimertinib will become the standard of care for first-line treatment, predicts Yu. Following the results of the phase III FLAURA trial, the FDA approved osimertinib as a first-line treatment for patients with non—small cell lung cancer whose tumors harbor 

 mutations (exon 19 deletions or exon 21 L858R substitution mutations).

Identifying resistance mutations is key when choosing a targeted therapy, as these treatments are very effective and they work for a long time. However, all patients progress at some point. Yu says that it is key to rebiopsy patients at that point, and to look and see what the different resistance mechanisms are. With osimertinib, there are patterns that are emerging, and off-target resistance is going to be a more dominant factor, Yu explains.

Helena A. Yu, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses treatments for EGFR-mutant lung cancer.

Helena A. Yu, MD

Articles

Role of Antibody-Drug Conjugates in NSCLC Treatment: Insights from EVOKE-02

Treatment Strategies for NSCLC with Non-Actionable Mutations

Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01

Dr Yu on the Investigation of BL-B01D1 in Lung Cancer

Dr. Yu on Treatments for EGFR-Mutant Lung Cancer