Khaled Hassan, MD, Khaled Hassan Laboratory, Cleveland Clinic Lerner Research Institute, discusses key results from the phase 1 CHRYSALIS trial (NCT02609776) of the bispecific antibody amivantamab-vmjw (Rybrevant) in non–small cell lung cancer (NSCLC) expressing 

In May 2021, the FDA approved amivantamab

 for the treatment of patients with locally advanced or metastatic NSCLC with 

 exon 20 insertion mutations who had progressed on or following platinum-based chemotherapy. This approval was based on findings from the non-randomized, open-label, dose-escalation and dose-expansion CHRYSALIS trial. The trial’s primary end points for dose escalation and expansion were overall response rate (ORR) and dose-limiting toxicity, Hassan begins. Key secondary end points included duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS).

Of the 81 efficacy-evaluable patients, amivantamab elicited an ORR of 40%, Hassan states. This included a complete response rate of 4% and a partial response rate of 36%. The median DOR with amivantamab was 11.1 months. Moreover, around 48% of patients exhibited stable disease, Hassan adds. The PFS and OS with amivantamab were 8.3 months and 22.8 months, respectively. These outcomes were improved compared with other standard of care of agents. Similarly, the CBR was 74% in patients who received the treatment.

The most common adverse effects (AEs) observed with amivantamab were infusion-related reactions, Hassan continues. Accordingly, investigators are attempting to move away from intravenous delivery towards subcutaneous delivery to mitigate these toxicities, Hassan notes. Other AEs included rash, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. These are all expected according to known safety signals with other EGFR-targeted therapies, Hassan details. The drug-related discontinuation rate was 4%, although 10% of patients experienced an AE leading to treatment discontinuation, Hassan concludes.

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Khaled Hassan, MD, discusses key results from the phase 1 CHRYSALIS trial of the bispecific antibody amivantamab-vmjw in non–small cell lung cancer expressing EGFR exon 20 insertion mutations.


Dr Hassan on the CHRYSALIS trial of Amivantamab in EGFR Exon 20–Mutated NSCLC

Khaled Hassan, MD, Khaled Hassan Laboratory, Cleveland Clinic Lerner Research Institute, discusses the importance of performing precise molecular profiling in patients with lung cancer and the need to identify individually tailored treatment approaches.

When performing molecular pathology for patients with lung cancer, it is important to recognize that not all mutations are the same, Hassan says. For example, if a patient presents with an 

 mutation, that does not necessarily mean that the patient has an activating mutation that is targetable with a specific treatment, Hassan emphasizes. Acquiring the specifics about a given patient’s mutation is vital to help inform treatment decisions, Hassan adds.

Once a specific mutation has been identified, it is also important to understand what targeted therapies are available to treat that patient, Hassan continues. Without comprehensive next-generation sequencing to look at all the specific mutations, it is difficult to identify a correct treatment, and there are also misconceptions about what specific mutations have targetable drugs, Hassan expands. Therefore, identifying the specific mutation and then understanding if there is a specific drug that targets it are crucial steps in managing treatment decisions for patients with lung cancer, Hassan explains.


With the growing number of targeted therapies available in the treatment of lung cancer, it is a new era of treatment for these patients, Hassan says. Lung cancer should no longer be treated as a single entity where chemotherapy-based treatments are the standard; rather, it is now vital to look at lung cancer on an individual level to determine the best course of treatment, Hassan notes.

By identifying any mutations driving tumors, patients with lung cancer can be classified into different subsets that have their own unique treatment options, Hassan says. By continuing to conduct molecular profiling for patients, treatment for lung cancer will continue to shift away from a one-size-fits-all approach, Hassan concludes.

Khaled Hassan, MD, discusses the importance of performing precise molecular profiling in patients with lung cancer and the need to identify individually tailored treatment approaches.

Dr. Hassan on the Importance of Accurate Molecular Profiling in Lung Cancer

Khaled A. Hassan, MD, MS, a medical oncologist at the University of Michigan Rogel Cancer Center, discusses the results of the FLAURA trial, which compared osimertinib (Tagrisso) with first-generation TKIs in patients with 

-mutant metastatic non—small cell lung cancer (NSCLC).

The FLAURA trial changed the management of patients with 

-driven cancers, explains Hassan. The trial showed a significant improvement in progression-free survival with osimertinib at 18.9 months versus 10.2 months with the first-generation EGFR TKIs erlotinib (Tarceva) or gefitinib (Iressa). There was also activity in patients with brain metastases compared with first-generation EGFR TKIs. Additionally, toxicity levels were low with osimertinib.

At the 2019 ESMO Congress, overall survival data showed a significant improvement with osimertinib at 38 months compared with 31 months with the first-generation TKIs. At 3 years, around 28% of patients were still taking osimertinib versus 9% of patients who received standard EGFR TKIs. These data solidify the role of osimertinib as a first-line treatment for patients with 

 mutations, meaning any trial looking at patients with 

-mutant NSCLC moving forward should have osimertinib as the control arm, Hassan concludes.

Khaled A. Hassan, MD, MS, discusses the results of the FLAURA trial, which compared osimertinib with first-generation TKIs in patients with EGFR-mutant metastatic non–small cell lung cancer.

Khaled A. Hassan, MD, MS

Articles

Dr Hassan on the CHRYSALIS trial of Amivantamab in EGFR Exon 20–Mutated NSCLC

Dr. Hassan on the Importance of Accurate Molecular Profiling in Lung Cancer

Dr. Hassan on FLAURA Trial Results in EGFR-Mutant NSCLC