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

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

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).

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer; NSCLC; Advanced Non-Small Cell Lung Cancer; NSCLC Stage IV; NSCLC Stage IIIB; Advanced Non-Small Cell Squamous Lung Cancer; Advanced Non-Small Cell Non-Squamous Lung Cancer
• Intervention / Treatment: Drug: MYTX-011

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Queen Elizabeth Hospital
    • Adelaide, South Australia, Australia, 5011
      • Cancer Research SA
• France
  • Bordeaux, France
    • Institut Bergonié-Bordeaux
  • Lyon, France
    • Centre Léon Bérard - Lyon
  • Marseille, France
    • APHM - Hopital de la Timone
  • Nantes, France
    • Institut de Cancérologie de l'Ouest (ICO institute)-St Herblain
  • Paris, France
    • INSTITUT Curie (lead)
  • Toulouse, France
    • Oncopole Claudius Regaud, IUCT-Oncopole
  • Villejuif, France
    • Gustave Roussy Institute
• South Korea
  • Busan, South Korea
    • Kosin Univ. Gospel Hospital
  • Incheon, South Korea, 21565
    • Chungbuk National Univ. Hospital
  • Seongnam, South Korea
    • Gachon University
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Severance Hospital
  • Seoul, South Korea, 03080
    • National Cancer Center
  • Suwon, South Korea
    • St. Vincent Hospital
  • MA
    • Seoul, MA, South Korea, 01886
      • Seoul National University Hospital
• Spain
  • Barcelona, Spain
    • Instituto Oncológico Dr Rosell (IOR) - Hospital Univ. Dexeus
  • Barcelona, Spain
    • START Barcelona-HM CIOCC Early Phase Program
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Madrid, Spain
    • START Centro Integral Oncologico Calra Campal
  • Málaga, Spain
    • Hospital Quironsalud Malaga
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia
  • Zaragoza, Spain
    • Hospital Universitario Lozano Blesa
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 110301
    • Taipei Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Cancer Centre
  • Zhubei, Taiwan, 302058
    • National Taiwan University Hospital Hsin-Chu Branch
  • MA
    • Taichung, MA, Taiwan, 01886
      • Taichung Veterans General Hospital
• United Kingdom
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, W1T 7HA
    • University College London Hospitals NHS Foundation Trust
  • Newcastle, United Kingdom
    • Newcastle upon Tyne Hospital (NHS)
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital - Oxford University Hospitals
• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Los Angeles, California, United States, 90095
      • UCLA
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Atlanta, Georgia, United States, 30318
      • Piedmont Physicians Medical Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine in St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Hollings Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology
  • Washington
    • Seattle, Washington, United States, 98019
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Cohorts A-D and F

1. Known to not have an actionable EGFR mutation. Subjects with or without other driver mutations 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 locally advanced/metastatic setting. Note: multiple TKIs for the same actionable mutation count as 1 line of therapy. Rechallenge of the same therapy regimen within 6 months of discontinuation date of the therapy is not considered a separate 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. The same rules above apply to all inclusion/exclusion criteria regarding prior lines of therapy.
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) and have not received more than 2 lines of prior systemic therapy in the locally advanced/metastatic setting.
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 and have not received more than 3 lines of prior systemic 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 targeting driver gene alteration and platinum-based chemotherapy, and also progressed on (or be considered ineligible for) or be intolerant to immune checkpoint inhibitor(as monotherapy or in combination with platinum-based chemotherapy, and have not received more than 3 lines of prior systemic therapy in the locally advanced/metastatic setting.
7. Subjects with MET exon 14 skipping mutation must have progressed on, or be intolerant to, at least one MET TKI if available, and have not received more than 2 lines of prior systemic therapy in the locally advanced/metastatic setting.

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 expression 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 non-squamous or adenosquamous NSCLC without EGFR mutation.
• Tumor sample with low cMET expression on tumor biopsy confirmed centrally by IHC that does not meet inclusion criteria for Cohorts A, B, or B2.

Cohort E:

• Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for a curative therapy), or metastatic NSCLC with actionable EGFR mutations.
• Tumor sample with high or intermediate cMET expression by IHC confirmed by central laboratory testing.
• Must have received an available standard of care therapy and have progressed on at least 1 and no more than 3 lines of prior systemic 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 cMET expression by IHC confirmed by central laboratory testing.
• Must have received an available standard of care therapy and have progressed on at least 1 line and no more than 3 lines of prior systemic therapy in the locally advanced/metastatic setting.

Cohort F

• Have histologically or cytologically confirmed locally advanced non-squamous or adenosquamous NSCLC without EGFR mutation.
• Have ultra-low cMET expression on tumor biopsy confirmed centrally by IHC that does not 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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation; Part 1 patients will receive MYTX-011.	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort A; 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; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort B; Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort C; Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort D; Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort E; Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort B2; Part 2 Cohort B2 patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort E2; Part 2 Cohort E2 patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.
Experimental: Part 2 Cohort F; Part 2 Cohort F patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011; MYTX-011 will be administered as an intravenous infusion every 21 days.

What is the study measuring?

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: 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
Part 1: Pharmacokinetic (PK) parameter (Total ADC)	Total ADC	24 months
Part 1: Pharmacokinetic (PK) parameter (Total antibody)	Total antibody	24 months
Part 1: Pharmacokinetic (PK) parameter (Free MMAE)	Free MMAE	24 months

Collaborators and Investigators

• Sponsor: Mythic Therapeutics
• Investigators: Study Director: Ting Wu, MD MSc, Mythic Therapeutics

Publications and helpful links

General Publications

• Gera N, Fitzgerald KM, Ramesh V, Patel P, Kanojia D, Colombo F, Kien L, Aoyama S, Xu L, Jean J, Deshpande AM, Comb WC, Chittenden T, Fiske BP. MYTX-011: A pH-Dependent Anti-c-MET Antibody-Drug Conjugate Designed for Enhanced Payload Delivery to c-MET-Expressing Tumor Cells. Mol Cancer Ther. 2024 Jun 10:OF1-OF12. doi: 10.1158/1535-7163.MCT-23-0784. Online ahead of print.
• Gera N, Fitzgerald KM, Ramesh V, Patel P, Kanojia D, Colombo F, Kien L, Aoyama S, Xu L, Jean J, Deshpande AM, Comb WC, Chittenden T, Fiske BP. MYTX-011: a pH-dependent anti-cMET antibody-drug conjugate designed for enhanced payload delivery to cMET expressing tumor cells. Mol Cancer Ther. 2024 Apr 30. doi: 10.1158/1535-7163.MCT-23-0784. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Actual): October 31, 2025
• Study Completion (Actual): November 7, 2025

Study Registration Dates

• First Submitted: November 29, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: MET; cMET; ADC; MYTX-011; Mythic; MYTX011; KisMET-01
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: MYTX-011-01; KisMET-01 (Other Identifier: Mythic Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: At the conclusion of the study
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No