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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 1 Multicenter Dose Escalation and Dose Expansion Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer - KisMET-01

Conditions
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NSCLC, NSCLC Stage IV, NSCLC Stage IIIB, Non-Small Cell Lung Cancer, Advanced Non-Small Cell Squamous Lung Cancer, Advanced Non-Small Cell Lung Cancer, Advanced Non-Small Cell Non-Squamous Lung Cancer

Intervention / Treatment
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* Drug: MYTX-011


Participation Criteria
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Eligibility Criteria
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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-C Known 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 therapy Patients 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 therapy All patients (Part 1 and Part 2) 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 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 medication Neuropathy > Grade 1 History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease. Active or chronic corneal disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Dose Escalation<br>Part 1 patients will receive MYTX-011. | Drug: MYTX-011<br>* MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.<br>|
| Experimental: Part 2 Cohort A<br>Part 2 Cohort A patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1. | Drug: MYTX-011<br>* MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.<br>|
| Experimental: Part 2 Cohort B<br>Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose. | Drug: MYTX-011<br>* MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.<br>|
| Experimental: Part 2 Cohort C<br>Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose. | Drug: MYTX-011<br>* MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.<br>|
| Experimental: Part 2 Cohort D<br>Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose. | Drug: MYTX-011<br>* MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.<br>|
| Experimental: Part 2 Cohort E<br>Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose. | Drug: MYTX-011<br>* MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of patients with dose limiting toxicity (DLT) | The dose limiting toxicities will be based on number and severity of treatment-related adverse events. | Up to Day 21 | 
| Part 2: Number of patients with tumor response | The overall response rate will be based on number of complete responses and partial responses. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Pharmacokinetic (PK) parameter | Total ADC | 24 months | 
| Part 1: Pharmacokinetic (PK) parameter | Total antibody | 24 months | 
| Part 1: Pharmacokinetic (PK) parameter | Free MMAE | 24 months | 
| Part 1: ADA | Presence of anti-drug antibodies | 24 months | 
| Part 1: ORR | Complete response + partial response | 24 months | 
| Part 1: DOR, TTR, DCR | Duration of response in patients that achieve CR or PR, time to response, best overall response and disease control rate | 2 years | 
| Part 1: PFS | Progression free survival | for up to 2 years after end of treatment | 
| Part 1: OS | Overall survival | for up to 2 years after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MET, cMET, MYTX-011, Mythic, MYTX011, ADC, KisMET-01