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

Inclusion Criteria:

Part 1:

• Histologically or cytologically confirmed locally advanced, recurrent or metastaticNSCLC 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 Cohorts A-D and F

1. Known to not have an actionable EGFR mutation. Subjects with or without other drivermutations are permitted to enroll.

2. Must have received (or be ineligible for) available standard of care therapy.

3. Must have progressed on at least 1 line of prior systemic therapy in the locallyadvanced/metastatic setting. Note: multiple TKIs for the same actionable mutationcount as 1 line of therapy. Rechallenge of the same therapy regimen within 6 monthsof discontinuation date of the therapy is not considered a separate line of therapy.Maintenance therapy is not considered a separate line of therapy. Adjuvant andneoadjuvant therapies count as 1 line of therapy if given within 6 months beforestudy entry. The same rules above apply to all inclusion/exclusion criteriaregarding prior lines of therapy.

4. Subjects without any actionable gene alteration: must have progressed on (or beconsidered ineligible for), or be intolerant to, platinum-based chemotherapy andimmune checkpoint inhibitor (as monotherapy or in combination with chemotherapy) andhave not received more than 2 lines of prior systemic therapy in the locallyadvanced/metastatic setting.

5. Subjects with actionable gene alterations (other than EGFR) for which immunecheckpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphomakinase [ALK] translocation): must have progressed on (or be considered ineligiblefor), or be intolerant to, anticancer therapy targeting driver gene alterations andplatinum-based chemotherapy and have not received more than 3 lines of priorsystemic therapy in the locally advanced/metastatic setting.

6. Subjects with actionable gene alterations (other than MET exon 14 skipping mutation)for which immune checkpoint inhibitor is standard of care: must have progressed on (or be considered ineligible for), or be intolerant to, anticancer therapy targetingdriver gene alteration and platinum-based chemotherapy, and also progressed on (orbe considered ineligible for) or be intolerant to immune checkpoint inhibitor(asmonotherapy or in combination with platinum-based chemotherapy, and have notreceived more than 3 lines of prior systemic therapy in the locallyadvanced/metastatic setting.

7. Subjects with MET exon 14 skipping mutation must have progressed on, or beintolerant to, at least one MET TKI if available, and have not received more than 2lines of prior systemic therapy in the locally advanced/metastatic setting.

Part 2:

Cohort A:

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for curative therapy), or metastatic non-squamous NSCLC without EGFRmutation.

• Tumor sample with high cMET expression by IHC confirmed by central laboratorytesting.

Cohort B:

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for curative therapy), or metastatic non-squamous NSCLC without EGFRmutation.

• Tumor sample with intermediate cMET expression by IHC confirmed by centrallaboratory testing.

Cohort B2

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for curative therapy), or metastatic non-squamous NSCLC without EGFRmutation.

• Tumor sample with intermediate cMET expression by IHC confirmed by centrallaboratory testing.

Cohort C:

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for curative therapy), or metastatic squamous NSCLC without EGFRmutation.

• Tumor sample with cMET expression by IHC confirmed by central laboratory testing.

Cohort D:

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for curative therapy), or metastatic non-squamous or adenosquamous NSCLCwithout EGFR mutation.

• Tumor sample with low cMET expression on tumor biopsy confirmed centrally by IHCthat does not meet inclusion criteria for Cohorts A, B, or B2.

Cohort E:

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for a curative therapy), or metastatic NSCLC with actionable EGFRmutations.

• Tumor sample with high or intermediate cMET expression by IHC confirmed by centrallaboratory testing.

• Must have received an available standard of care therapy and have progressed on atleast 1 and no more than 3 lines of prior systemic therapy in the locallyadvanced/metastatic setting.

Cohort E2

• Have histologically or cytologically confirmed locally advanced, recurrent (and nota candidate for curative therapy), or metastatic NSCLC with actionable EGFRmutations.

• Tumor sample with high or intermediate cMET expression by IHC confirmed by centrallaboratory testing.

• Must have received an available standard of care therapy and have progressed on atleast 1 line and no more than 3 lines of prior systemic therapy in the locallyadvanced/metastatic setting.

Cohort F

• Have histologically or cytologically confirmed locally advanced non-squamous oradenosquamous NSCLC without EGFR mutation.

• Have ultra-low cMET expression on tumor biopsy confirmed centrally by IHC that doesnot meet inclusion criteria for Cohorts A,B, B2, or D.

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 thestudy 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 protocolrequirements

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 withsystemic steroids or evidence of active interstitial lung disease or pneumonitis. Ahistory of prior radiation pneumonitis in the radiation field (fibrosis) ispermitted.

• Clinically significant systemic illness that could pose undue risk to the subject orconfound the ability to interpret study results.

• Active infection requiring IV antibiotics, antivirals, or antifungal medicationwithin 14 Days of Cycle 1 Day 1

• Neuropathy > Grade 1

• History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or otherclinically significant liver disease.

• Active or chronic corneal disorder

• Conditions that may interfere with assessment of vision, such as monocular status orsevere visual impairment in 1 or both eyes