ASCO 2021: Non-Small Cell Lung Cancer Special Session-Oral Report (02)

Abstract introduction 5

Biomarker tissue study of untreated metastatic non-small cell lung cancer (m NSCLC ) patients (pts) in the practice of the American Oncology Network community

DOI: 10.

In view of the importance of molecular testing and targeted therapy to mNSCLC, MYLUNG (Molecular Information Lung Cancer Therapy in Community Cancer Network) Consortium Practical Research has evaluated more than 1,000 suppliers across the United States within the American Oncology Network.

This is a retrospective observational chart study of mNSCLC patients who started first-line (1L) system therapy from January 4, 2018 to March 31, 2020.

We identified 3474 adults.

This real-world study showed that most patients received at least one biomarker test before 1L, but <50% of patients received all 5 tests.

Abstract Introduction 6

Ethnic differences in non-small cell lung cancer (NSCLC) biomarker testing and clinical trial registration

DOI: 10.

Race differences in cancer may exist at many levels of the healthcare system, from screening to timely diagnosis and treatment, and clinical trial registration.

This retrospective observational study utilized the Flatiron Health database, which included longitudinal data on patients with advanced/metastatic NSCLC.

A total of 14,768 patients were eligible: 9,793 (66.

The NGS-based test recommended by the National Comprehensive Cancer Network Oncology Clinical Guidelines for patients with advanced/metastatic NSCLC is the most significant difference among black patients, with a difference of more than 10% in acceptance of the test.

Abstract Introduction 7

Combination of Amivantamab and lazertinib for the treatment of non-small cell lung cancer (NSCLC) and potential response biomarkers for osimertinib relapsed, EGFR mutation (EGFRm) not receiving chemotherapy

DOI: 10.

Amivantab (an EGFR-MET bispecific antibody) and lazertinib (a third-generation tyrosine kinase inhibitor) were observed in newly treated and relapsed EGFRm NSCLC patients (pts) with osimertinib (osi) The initial efficacy of the combination.

NSCLC patients with EGFR exon 19 deletion or L858R mutation who did not undergo chemotherapy after receiving OSI were included in the combination cohort of the ongoing CHRYSALIS study (NCT02609776).

Among 45 patients with recurrence of osi, 36% (95% CI, 22-51) had a confirmed response (1 complete response and 15 partial response [PR]).

Combination treatment with amivantamab and lazertinib responded in 36% of patients who did not receive chemotherapy who had progressed osi.

Abstract Introduction 8

Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor resistance, EGFR mutation (EGFR m) non-small cell lung cancer (NSCLC)

DOI: 10.

After the failure of EGFR TKI and platinum-based chemotherapy (PBC), treatment options for patients with advanced EGFR m NSCLC (pts) are limited.
HER3-DXd is an antibody-drug conjugate consisting of a fully human monoclonal antibody directed against HER3 connected to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker.
We previously introduced the efficacy/safety data of an ongoing study of HER3-DXd in EGFR m NSCLC after EGFR TKI treatment failure (median follow-up time, 5.
4 months).
We are now conducting extended follow-up for patients receiving the recommended dose (5.
6 mg/kg IV Q3W).

This phase 1 dose escalation/expansion study included patients with locally advanced or metastatic EGFR m NSCLC who had previously received EGFR TKI therapy (NCT03260491).
Allow patients with stable brain metastases (BM).
According to RECIST v1.
1, the primary endpoint was blinded Independent Central Review (BICR) to confirm ORR; secondary endpoints included DOR, PFS, and safety.

In the study, 57 patients received HER3-DXd 5.
6 mg/kg intravenous Q3W treatment; median follow-up, 10.
2 months.
The median of previous anti-cancer regimens was 4.
100% had received EGFR TKI treatment (86% had received osimetinib [OSI]), and 91% had received PBC treatment.
47% had a history of BM.
The median duration of treatment was 5.
5 months; 18 patients (32%) were receiving treatment.
The ORR confirmed by BICR was 39%, and 14/22 reactions occurred within 3 months of starting HER3-DXd.
The DCR was 72% (95% CI, 58.
5%-83.
0%).
The median DOR was 6.
9 months (95% CI, 3.
1 mo-NE), and the median PFS was 8.
2 months (95% CI, 4.
4-8.
3 months).
Anti-tumor activity has been observed in different EGFR TKI resistance mechanisms, including those that are not directly related to HER3 (EGFR C797S, MET, or HER2 amp and BRAF fusion).
In patients with previous PBC, ORR was 37% (19/52; 95% CI, 23.
6%-51.
0%); in patients with previous OSI and PBC, ORR was 39% (17/44; 95% CI , 24.
4%-54.
5%).
Of the 43 patients whose expression of HER3 can be assessed, almost all of them expressed HER3; the median H-score of membranes passing IHC was 180 (range, 2-280).
The median H score (range; N) of CR/PR patients was 195 (92-268; 15), SD patients were 180 (4-280; 15), PD patients were 126.
5 (2-251; 6), none The patient with the best overall response value was 180 (36-180; 7).
The most common ≥ grade 3 adverse events (AEs) were thrombocytopenia (30%), neutropenia (19%), and fatigue (14%).
4 patients (7%; 1 patient ≥ grade 3 [2%]; no grade 5) developed drug-related interstitial lung disease as determined by the central government.
Six of 57 patients (11%) had AEs related to treatment discontinuation (no one was due to thrombocytopenia).

HER3-DXd 5.
6 mg/kg IV Q3W shows anti-tumor activity in various EGFR TKI resistance mechanisms of metastatic/locally advanced EGFR m NSCLC after extensive pretreatment.
The security is consistent with the previous report.
After the failure of EGFR TKI and PBC, a phase 2 study of HER3-DXd in EGFR m NSCLC patients has been initiated (NCT04619004).

Summary Introduction 9

DZD9008 having Exon20 EGFR NSCLC insertional mutagenesis 1 patient in preliminary safety and efficacy results of the study

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
9008

There is no approved targeted therapy for EGFR exon 20 insertion (exon20ins) mutant NSCLC.
DZD9008 is a reasonably designed selective and irreversible EGFR exon20ins inhibitor, which is being studied in two ongoing phase 1/2 studies (NCT03974022 and CTR20192097).

The purpose of these studies is to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of DZD9008 for NSCLC with EGFR or HER2 mutations.
Both studies included dose escalation and expansion cohorts.
Meta-analysis was used to define the recommended phase 2 dose (RP2D).

Between July 9, 2019 and February 5, 2021, 97 NSCLC patients with EGFR or HER2 mutations took DZD9008 (dose range: 50 mg to 400 mg, once a day).
Male/Female: 44/53; 59 people have EGFR exon 20.
DZD9008 is well tolerated, up to 400 mg (MTD), once a day.
DLTs are diarrhea and arrhythmia .
The most common TEAEs are diarrhea (grade 3, 5.
2%) and rash (grade 3, 1%).
DZD9008 showed a PK similar to the dose ratio, with a half-life of about 50 hours.
56 patients with more than 16 different EGFR exon 20ins mutations had more than one treatment efficacy evaluation.
Previous treatment: median 2 (range 1-10), previous chemotherapy 92.
9% (52/); previous TKI 44.
6% (25/56), including 1 patient who had received Pozzini therapy; 42.
9% (24/ 56) There is brain metastasis.
Partial responses were observed at dose levels ≥100 mg.
When the RP2D dose is 300 mg, once a day, the objective response rate is 48.
4% (15/31), and the disease control rate (DCR) is 90.
3% (28/31).
Two patients who had previously been treated with JNJ-61186372 responded.
Anti-tumor activity was observed in different EGFR exon 20ins mutation subtypes.
According to the data cutoff, the median treatment time was 100 days (range 1-422).
The longest response time was more than 6 months, and 18 of the 22 respondents were still responding.

DZD9008 shows good safety and promising anti-tumor efficacy in pretreatment NSCLC with EGFR exon20ins mutation.
The updated data will be announced at the meeting.
DZD9008 is currently in phase II clinical development (NCT03974022).