New data from the phase 1 CHRYSALIS study, which has evaluated Amivantamab in patients with metastatic or unresectable non-small cell lung cancer ( NSCLC ) and epidermal growth factor receptor ( EGFR ) exon 20 insertion mutations whose disease progressed on or after Platinum-based chemotherapy, were presented at the International Association for the Study of Lung Cancer's ( IASLC ) 2020 World Conference on Lung Cancer ( WCLC ) Singapore.
The key findings showed robust activity and durable responses with a tolerable and manageable safety profile in patients with NSCLC and EGFR exon 20 insertion mutations, a mutation for which no targeted therapies are currently approved.
Amivantamab is an investigational, fully-human EGFR and MET bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR and MET mutations and amplifications.
In CHRYSALIS study, investigators have assessed the efficacy and safety of Amivantamab in patients with NSCLC and EGFR exon 20 insertion mutations, who had progressed on prior Platinum-based chemotherapy, and were treated at the recommended phase 2 dose ( RP2D of 1050 mg [ 1400 mg for a patient weight of 80 kg or more ] Amivantamab ).
Disease response using overall response rate ( ORR ), per RECIST v1.1 was the primary endpoint. Other endpoints included duration of response ( DOR ), clinical benefit rate, progression-free survival ( PFS ) and overall survival ( OS ).
In the post-Platinum efficacy cohort ( n=81 ), the ORR as assessed by blinded independent central review was 40% ( n=32; 95% confidence interval [ CI ], 29 – 51 ), with three patients ( 4% ) having complete responses and 29 patients ( 36% ) achieving partial responses ( PR ).
Responses were durable with median duration of response of 11.1 months ( 95% CI, 6.9 – not reached ) with 20 patients ( 63% ) having responses of at least six months or greater duration.
Median progression-free survival was 8.3 months ( 95% CI, 6.5 – 10.9 ) and median overall survival was 22.8 months ( 95% CI, 14.6 – not reached ).
The clinical benefit rate ( greater than or equal to PR or stable disease 11 weeks or more ) was 74% ( 95% CI, 63 – 83 ).
Among patients treated with Amivantamab monotherapy ( n=114 ) at the RP2D, the most common treatment emergent adverse events were rash ( 86% ), infusion-related reactions ( IRR; 66% ) and paronychia ( 45% ).
Additional adverse effects were stomatitis ( 21% ) and pruritus ( 17% ).
Grade greater than or equal to 3 adverse effects were reported in 35% of patients, of which 16% were considered treatment-related with rash ( 4% ) and IRR ( 3% ) being most frequent.
No treatment-related deaths were reported.
The incidence of treatment-related adverse effects leading to dose reduction and discontinuation was 13% and 4%, respectively.
EGFR mutations, leading to uncontrolled cancer cell growth and division, are some of the most common mutations in NSCLC.
EGFR exon 20 insertion mutations are the third most prevalent primary EGFR mutation and account for at least 9% of all EGFR mutations.
These mutations, however, often go undetected because of the limited use of Next Generation Sequencing ( NGS ) testing. Polymerase chain reaction ( PCR ) genetic testing is projected to miss 50% or more of tumors with EGFR exon 20 mutations.
The cancer driven by EGFR exon 20 insertion mutations is generally insensitive to approved EGFR tyrosine kinase inhibitor ( TKI ) treatments and carries a worse prognosis compared with cancer driven by more common EGFR mutations, including exon 19 deletions/L858R substitutions.
After 34-months median follow-up, patients with EGFR exon 20 insertion mutations experienced a 75% increased risk of death.
The five-year survival rate for exon 20 insertion mutations is 8% compared to 19% for other EGFR mutations. ( Xagena )
Source: Janssen Pharmaceutical, 2021