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).

The study will be conducted in 2 parts. Part 1 will assess the safety and tolerability of MYTX-011 and identify the dose to be studied in Part 2. Part 2 will include subjects with NSCLC with cMET overexpression or MET amplification/exon 14 skipping mutations, populations with a current unmet medical need.

Eligibility Criteria:
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 without EGFR mutation.
* 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 without EGFR mutation.
* Tumor sample with intermediate cMET expression by IHC confirmed by central laboratory testing.

Cohort B2

* Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC without EGFR mutation.
* 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 without EGFR mutation.
* Tumor sample with cMET overexpression by IHC confirmed by central laboratory testing.

Cohort D:

* Have histologically or cytologically confirmed locally advanced non-squamous or adenosquamous NSCLC without EGFR mutation.
* Tumor sample with low cMET expression on tumor biopsy confirmed centrally

that does not meet cMET IHC entry criteria for Cohorts A,B, or B2-C

Cohort E:

- curative therapy), or metastatic NSCLC with actionable EGFR mutations

Tumor sample with high or intermediate cMETet expression tumor biopsy confirmed centrally

Must have received an available standard of care therapy and have progressed on at least 1 line of prior therapy in the locally advanced/metastatic setting.

Cohort E2

-Have histologically or cytologically confirmed locally advanced, recurrent

(and not a candidate for curative therapy), or metastatic NSCLC with actionable EGFR mutations.

• Tumor sample with high or intermediate cMEet expression tumor biopsy confirmed centrally

Must have received an available standard of care therapy and have progressed on at least 1 line of prior therapy in the locally advanced/metastatic setting.

Part 2 Cohorts A-D

1. Known to not have an actionable EGFR mutation. Subjects with or without other driver mutations are permitted to enroll.
2. Must have received available standard of care therapy.
3. Must have progressed on at least 1 line of prior therapy in the locally advanced/metastatic setting. Note: multiple lines of TKI for the same actionable mutation count as 1 line of therapy. Maintenance therapy is not considered a separate line of therapy. Adjuvant and neoadjuvant therapies count as 1 line of therapy if given within 6 months before study entry.
4. Subjects without any actionable gene alteration: must have progressed on (or be considered ineligible for), or be intolerant to, platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).
5. Subjects with actionable gene alterations (other than EGFR) for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase \[ALK\] translocation): must have progressed on (or be considered ineligible for), or be intolerant to, anticancer therapy targeting driver gene alterations and platinum-based chemotherapy.
6. Subjects with actionable gene alterations (other than EGFR) for which immune checkpoint inhibitor is standard of care: must have progressed on (or be considered ineligible for), or be intolerant to, anticancer therapy targeting driver gene alteration and platinum-based chemotherapy, and also progressed on (or be considered ineligible for) or be intolerant to immune checkpoint

All patients (Part 1 and Part 2)

Inclusion Criteria:

* Patient has at least one measurable lesion per RECIST 1.1
* ECOG performance status 0 or 1
* For 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 requirements

Exclusion Criteria:

Radiation to the lung within 6 weeks prior to screening. For all other sites (except lung), therapeutic or palliative radiation within 2 weeks prior to the first dose of study drug. Must have recovered from all radiation-related toxicity.

Major surgery within 28 days of first dose of study drug administration.

Untreated, uncontrolled central nervous system (CNS) metastases and/or leptomeningeal disease.

* 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 medication within 14 Days of Cycle 1 Day 1
* Neuropathy \> Grade 1
* History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease.
* Active or chronic corneal disorder
* Conditions that may interfere with assessment of vision, such as monocular status or severe visual impairment in 1 or both eyes