- |||||||||| tigozertinib (BLU-945) / Blueprint Medicines, Gilotrif (afatinib) / Boehringer Ingelheim, mavelertinib (PF-06747775) / Pfizer
Next-generation NSCLC drug development powered by PDCs and PDOs: Mimicking real responses (Section 4; Poster Board No: 7) - Mar 25, 2025 - Abstract #AACR2025AACR_8476;
Another example is YUO-143, which harbors EGFR mutations E19del/T790M/C797S and was derived from a patient resistant to gefitinib and mavelertinib. YUO-143 was used in the development of the 4th gen TKI, BLU-945, and showed an IC50 of 43 nM.Conclusions : Patient-derived models could serve as a crucial tool in developing novel therapeutic strategies and next-generation drugs for NSCLC.
- |||||||||| tigozertinib (BLU-945) / Blueprint Medicines, Gilotrif (afatinib) / Boehringer Ingelheim, mavelertinib (PF-06747775) / Pfizer
Patient-derived cells (PDCs) and organoids (PDOs) as critical platforms for developing next therapeutic strategies for NSCLC (Section 29) - Mar 5, 2024 - Abstract #AACR2024AACR_4104;
IC50 of YUO-139 and YU-1092 to afatinib were 2.1 nM and 23.8 nM respectively. YUO-143 is a PDO model that harbors EGFR E19del/T790M/C797S which was derived from gefitinib and mavelertinib resistant patient revealed sensitivity to BLU-945 (IC50, 43 nM), a novel fourth-generation EGFR-TKI.Conclusions : Patient derived models could be a critical tool for developing therapeutic strategies for NSCLC.
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Journal: Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy. (Pubmed Central) - Jul 23, 2022
Mavelertinib, dosed as low as 5 mg/kg of body weight or as high as 50 mg/kg, was efficacious in the acute murine Giardia infection model. These results suggest that mavelertinib merits consideration for repurposing and advancement to giardiasis clinical trials while its analogues are further developed.
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Phase classification, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Jun 10, 2021
P1/2, N=65, Terminated,
PF-06747775 had a manageable safety profile and the study design highlights important considerations for future anti-EGFR agent development. Phase classification: P2 --> P1/2
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Review, Journal: Beyond osimertinib: The development of 3-generation EGFR Tyrosine Kinase Inhibitors. (Pubmed Central) - May 25, 2021
P3
Additionally, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, maverlertinib) including phase 3 results of rociletinib and naquotinib. We further profiled the next-generation combination clinical trial design of third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704) and ACROSS2 (NCT04500717).
- |||||||||| Tagrisso (osimertinib) / AstraZeneca, mavelertinib (PF-06747775) / Pfizer
Journal: Complex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands. (Pubmed Central) - Dec 19, 2020
Here, we present the first complex crystal structures of mutant EGFR in complex with third-generation inhibitors such as osimertinib and mavelertinib in the presence of simultaneously bound allosteric inhibitors. These structures highlight the possibility of further combinations targeting EGFR and lay the foundation for hybrid inhibitors as next-generation TKIs.
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Trial termination, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Aug 31, 2020
P2, N=65, Terminated,
Completed --> Terminated; The study was ended for strategic reasons and changes in the external environment. The safety profile and risk benefit ratio for PF-0674775 remained unchanged.
- |||||||||| Review, Journal: Novel Third-Generation EGFR Tyrosine Kinase Inhibitors and Strategies to Overcome Therapeutic Resistance in Lung Cancer. (Pubmed Central) - Dec 21, 2019
The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance...Drug development has been breathtaking in this space with other third-generation compounds at various stages of development: rociletinib (CO-1686), olmutinib (HM61713), nazartinib (EGF816), naquotinib (ASP8273), mavelertinib (PF-0647775), and AC0010...Strategies to understand and predict patterns of mutagenesis are still in their infancy; however, technologies to understand synthetically lethal dependencies and track cancer evolution through therapy are being explored. The expansion of combinatorial therapies is a direction forward targeting minimal residual disease and bypass pathways early based on projected resistance.
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Trial primary completion date, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Jul 5, 2019
P2, N=65, Active, not recruiting,
The expansion of combinatorial therapies is a direction forward targeting minimal residual disease and bypass pathways early based on projected resistance. Trial primary completion date: Dec 2019 --> Jan 2019
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Trial completion date, Trial primary completion date, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Sep 25, 2018
P2, N=65, Active, not recruiting,
Trial primary completion date: Dec 2019 --> Jan 2019 Trial completion date: Jul 2022 --> Mar 2020 | Trial primary completion date: Mar 2021 --> Dec 2019
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Enrollment closed, Enrollment change, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Jul 17, 2018
P2, N=65, Active, not recruiting,
Trial completion date: Jul 2022 --> Mar 2020 | Trial primary completion date: Mar 2021 --> Dec 2019 Recruiting --> Active, not recruiting | N=159 --> 65
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Trial completion date, Trial initiation date, Trial primary completion date, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Mar 3, 2018
P2, N=159, Recruiting,
Recruiting --> Active, not recruiting | N=159 --> 65 Trial completion date: Apr 2022 --> Jul 2022 | Initiation date: May 2015 --> May 2015 | Trial primary completion date: Dec 2020 --> Mar 2021
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Trial primary completion date, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Jan 17, 2018
P2, N=159, Recruiting,
Trial completion date: Apr 2022 --> Jul 2022 | Initiation date: May 2015 --> May 2015 | Trial primary completion date: Dec 2020 --> Mar 2021 Trial primary completion date: Sep 2020 --> Dec 2020
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Enrollment change, Trial primary completion date, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Oct 27, 2016
P1/2, N=159, Recruiting,
Phase classification: P1/2 --> P2 N=200 --> 159 | Trial primary completion date: May 2019 --> Oct 2019
- |||||||||| mavelertinib (PF-06747775) / Pfizer
Trial primary completion date, PD(L)-1 Biomarker, Metastases: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M) (clinicaltrials.gov) - Oct 3, 2016
P1/2, N=200, Recruiting,
N=200 --> 159 | Trial primary completion date: May 2019 --> Oct 2019 Trial primary completion date: Apr 2018 --> May 2019
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