Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer

This is a Phase I open label multi-center study to evaluate the safety, tolerability, pharmacokinetics and preliminary effectiveness of the investigational drug MYTX-011 in patients with locally advanced, recurrent or metastatic NSCLC. MYTX-011 is in a class of medications called antibody drug conjugates (ADCs). MYTX-011 is composed of a pH-dependent anti-cMET antibody and the potent antimicrotubule drug monomethyl auristatin E (MMAE).

Inclusion Criteria:Part 1:Histologically or cytologically confirmed locally advanced, recurrent or metastatic NSCLC and have received available standard of care therapy.There is no limit on the number of prior therapies that can have been received.Part 2:Cohort A:Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC.Tumor sample with high cMET expression by IHC confirmed by central laboratory testing.Cohort B:Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC.Tumor sample with intermediate cMET expression by IHC confirmed by central laboratory testing.Cohort C:Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic squamous NSCLC.Tumor sample with cMET overexpression by IHC confirmed by central laboratory testing.Cohort D:Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC.Tumor sample that does not meet cMET IHC entry criteria for Cohorts A-CKnown MET amplification or exon 14 skipping mutations respectively. Patients with MET exon 14 skipping mutations must have received MET TKI therapy if available and considered standard of care.Cohort E:Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC.Evidence of cMET expression by IHC as documented in medical records.No more than 3 prior lines of systemic therapy including prior cMET targeted ADC or antibody.Part 2 Cohorts A-D- No more than two prior lines of therapy in the locally advanced/metastatic setting.Part 2 Cohorts A-E:Known to not have an actionable EGFR mutation. Patients with or without other driver mutations are permitted to enroll.Patients without any actionable gene alteration: must have progressed on (or be considered ineligible for) standard of care therapyPatients with actionable gene alterations (other than EGFR) must have progressed on (or be considered ineligible for) or be intolerant to anti-cancer therapy targeting driver gene alterations and available standard of care therapyAll patients (Part 1 and Part 2)Patient has at least one measurable lesion per RECIST 1.1ECOG performance status 0 or 1For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective method of birth control for the duration of the study treatment and for at least 6 months after the last dose of study drug.Able to provide informed consent, and willing and able to comply with study protocol requirementsExclusion Criteria:Radiation to the lung within 2 months prior to screening.Major surgery within 28 days of first dose of study drug administration.Untreated, uncontrolled CNS metastases.History of interstitial lung disease or pneumonitis that required treatment with systemic steroids or evidence of active interstitial lung disease or pneumonitis. A history of prior radiation pneumonitis in the radiation field (fibrosis) is permitted.Clinically significant systemic illness that could pose undue risk to the subject or confound the ability to interpret study results.Active infection requiring IV antibiotics, antivirals, or antifungal medicationNeuropathy > Grade 1History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease.Active or chronic corneal disorder