EGFR T790M negative

P1, N=69, Recruiting, Emory University | Phase classification: P1b --> P1 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

This study indicates that ddPCR may contribute as a supplement to NGS in liquid biopsies for T790M detection in EGFR-TKIs relapsed patients and help to optimize the treatment strategies, especially for those without coexistence of EGFR-sensitive mutation. www.clinicaltrials.gov identifier is NCT05458726.

P2, N=86, Terminated, Jiangsu Simcere Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 --> Jul 2023 | Recruiting --> Terminated; The study was terminated due to the sponsor's research and development strategy adjustment.

P1, N=18, Completed, University of Cologne | Recruiting --> Completed | Trial completion date: Apr 2023 --> Nov 2023

P1/2, N=43, Active, not recruiting, MedImmune LLC | Phase classification: P1b/2 --> P1/2 | Trial completion date: Sep 2024 --> Jan 2025

P2, N=73, Completed, Samsung Medical Center | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Oct 2023

P=N/A, N=20, Recruiting, Hunan Province Tumor Hospital | Not yet recruiting --> Recruiting

NGS after EGFR-TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR-TKI resistance may find more patients with targetable cancers.

P=N/A, N=20, Not yet recruiting, Hunan Province Tumor Hospital | Trial completion date: Nov 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Dec 2024

P2, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=55 --> 35

No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.

P=N/A, N=20, Not yet recruiting, Hunan Province Tumor Hospital

P2, N=55, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=65, Active, not recruiting, Samsung Medical Center | Enrolling by invitation --> Active, not recruiting

Real-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions.

She was treated with intrathoracic infusion chemotherapy (pemetrexed 200mg+nedaplatin 20mg) on October 11, 2018...Based on the above findings, the patient was administered with gefitinib 250 mg daily as first-line therapy on November 15, 2018, and achieved partial response (PR)...On January 25, 2022, the patient was hospitalized for shortness of breath, and received intrathoracic Infusion chemotherapy (cisplatin 80mg)... The combination therapy of afatinib and osimertinib could be a new therapeutic option for patients with lung adenocarcinoma harboring EGFRG724S/T790M/19Del mutation.

Patient received erlotinib 150 mg daily as frontline treatment in December 2018. We present the case of a patient with advanced stage NSCLC, with EGFR mutation, Secondary T790M positive and MET amplification, received osimertinib and capmatinib as third-line treatment. The efficacy was different from previous report (1), using both combination in EGFR mutation, T790M negative, MET-amplified patient, emphasizing the marginal effect in this subgroup.

We conducted a phase II study aimed to determine the efficacy and tolerability of dual ICI therapy, durvalumab and tremelimumab, with platinum‐pemetrexed chemotherapy, in metastatic EGFR mutant lung cancer following progression with EGFR TKIs. This international, non-comparative, two-cohort study enrolled adults from 10 Australian and 6 Taiwanese sites. Eligible participants were assigned to study cohort 1 (EGFR exon 20 T790M negative on tissue and plasma; progression on first-line osimertinib or following single line of 1st/2nd generation TKI) or cohort 2 (T790M positive on tissue and/or plasma; progression on ≥1 lines of TKI including osimertinib)... Durvalumab and tremelimumab with chemotherapy demonstrated promising anti-tumor activity, particularly in EGFR T790M negative tumors. The safety profile was consistent with known AEs with chemoimmunotherapy in advanced lung cancer.

P1b/2, N=43, Active, not recruiting, MedImmune LLC | Trial completion date: Jan 2024 --> Sep 2024

P1, N=138, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease. This was the first success case in Japan where a clinical trial was initiated based on a patient's proposal.

P2, N=55, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2023 --> Dec 2023

Tissue T790M result appeared more predictive of osimertinib efficacy compared to plasma, highlighting potential T790M heterogeneity and the advantage with paired tumor-plasma T790M testing at TKI resistance. T790M- disease at resistance remains an unmet treatment need.

EGFR-mutated patients who received ICIs combined with anti-angiogenic therapy had longer PFS and OS than patients with ICIs combined with chemotherapy. Patients with L858R or without T790M mutation benefited more from ICI combinations. Besides, patients with prior first-generation EGFR-TKI resistance could benefit more from ICIs combinations than prior third-generation EGFR-TKI resistance patients.

P2/3, N=14, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Active, not recruiting --> Recruiting

Forty-five percent of pts received afatinib as first line treatment, followed by 42.5% of gefitinib and 12.5% of erlotinib. Lazertinib has substantial CNS activity regardless of T790M status against the progression of intracranial metastases ± LM during the treatment of 1st or 2nd-G EGFR-TKIs in metastatic EGFR M+ NSCLC pts. These results suggest that using lazertinib instead of brain local treatment would be a potential strategy in EGFR M+ NSCLC, who progressed on CNS metastases after prior EGFR-TKI. Clinical trial information: NCT05326425.

P2/3, N=14, Active, not recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | N=50 --> 14

No abstract available

P1b, N=69, Recruiting, Emory University | Trial completion date: Dec 2024 --> Dec 2025

P1b/2, N=43, Active, not recruiting, MedImmune LLC | Trial completion date: Dec 2022 --> Jan 2024

Background Although osimertinib has been approved as first-line therapy, 1st or 2nd generation EGFR TKIs are still being used as first-line therapy...Results In total, 63 patients retreated with gefitinib (n = 34) or erlotinib (n = 29) after the progression of 2nd or more line chemotherapy...Conclusions Retreatment with EGFR-TKIs can be considered an option after the failure of chemotherapy for patients who were previously controlled by EGFR-TKI. The 1st generation EGFR TKIs retreatment may induce T790M mutation (32%) in patients who had not previously T790M mutation, leading to 3rd generation EGFR TKI sequential treatment and eventually prolong OS.

Repeat rebiopsy can increase the T790M mutation positivity rate. Osimertinib showed similar efficacy and safety in T790M-positive patients whether detected by the first or repeat rebiopsy.

Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.

P3, N=6, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Novartis decided to halt enrolment for this study on 11-May-2022. This decision was based on a business decision and not related with any safety concerns.

Oleclumab plus osimertinib showed evidence of moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.

In 19/55 randomized pts (34.5%) with METamp (GCN ≥5, n=18; MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), median age was 60.4 years, 68.4% were never-smokers, and prior EGFR inhibitors were gefitinib (57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). Tepotinib + gefitinib improved PFS and OS vs CT in pts with EGFR-m NSCLC with METamp. INSIGHT 2 is evaluating tepotinib + osimertinib in this setting

Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs.

P3, N=6, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: May 2022 --> Dec 2022

In 19/55 randomized patients (34.5%) with METamp (GCN ≥5, n=18; MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), the median age was 60.4 years, 68.4% were never-smokers, and prior EGFR inhibitors were gefitinib (57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). Tepotinib + gefitinib significantly improved PFS and OS versus chemotherapy in patients with EGFR-mutant NSCLC with METamp.

The most frequent resistance mechanism to 1-2gen TKIs is EGFR T790M mutation, which is targeted by osimertinib...In our study population, the overall T790M prevalence-detected with both LB and TB-was 42.7%. Repeated LB testing can be useful in a real-life scenario to detect EGFR T790M mutation.

All grade 1-2 according to CTCAE v5.0 except one patients discontinued treatment due to musculoskeletal pain Table: 377P Conclusions As second-line therapy, this study confirmed the efficacy of aumolertinib for T790M-positive patients with a satisfied safety profile and mPFS up to 16 months in real world. And to our knowledge, this was the first report about clinical activity of aumolertinib in T790M-negative patients.