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

NCT ID: NCT05652868

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 227 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-23
• Study Completion Date: 2025-11-07

Brief Summary

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

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 Dose Escalation

Part 1 patients will receive MYTX-011.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

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.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

Part 2 Cohort B

Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

Part 2 Cohort C

Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

Part 2 Cohort D

Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

Part 2 Cohort E

Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

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

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

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

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

Part 2 Cohort F

Part 2 Cohort F patients will receive MYTX-011 at the recommended phase 2 dose.

Group Type: EXPERIMENTAL

MYTX-011

Intervention Type: DRUG

MYTX-011 will be administered as an intravenous infusion every 21 days.

Interventions

MYTX-011

MYTX-011 will be administered as an intravenous infusion every 21 days.

Intervention Type: DRUG

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 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.

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.

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

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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mythic Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ting Wu, MD MSc

Role: STUDY_DIRECTOR

Mythic Therapeutics

Locations

University of California San Diego

La Jolla, California, United States

UCLA

Los Angeles, California, United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Piedmont Physicians Medical Oncology

Atlanta, Georgia, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Atlantic Health System

Morristown, New Jersey, United States

NYU Langone Medical Center

New York, New York, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

MUSC Hollings Cancer Center

Charleston, South Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology

Fairfax, Virginia, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Blacktown Hospital

Blacktown, New South Wales, Australia

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Queen Elizabeth Hospital

Adelaide, South Australia, Australia

Cancer Research SA

Adelaide, South Australia, Australia

Institut Bergonié-Bordeaux

Bordeaux, , France

Centre Léon Bérard - Lyon

Lyon, , France

APHM - Hopital de la Timone

Marseille, , France

Institut de Cancérologie de l'Ouest (ICO institute)-St Herblain

Nantes, , France

INSTITUT Curie (lead)

Paris, , France

Oncopole Claudius Regaud, IUCT-Oncopole

Toulouse, , France

Gustave Roussy Institute

Villejuif, , France

Seoul National University Hospital

Seoul, MA, South Korea

Kosin Univ. Gospel Hospital

Busan, , South Korea

Chungbuk National Univ. Hospital

Incheon, , South Korea

Gachon University

Seongnam, , South Korea

National Cancer Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

St. Vincent Hospital

Suwon, , South Korea

Instituto Oncológico Dr Rosell (IOR) - Hospital Univ. Dexeus

Barcelona, , Spain

START Barcelona-HM CIOCC Early Phase Program

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

START Centro Integral Oncologico Calra Campal

Madrid, , Spain

START Madrid-FJD, Hospital Fundación Jiménez Díaz

Madrid, , Spain

Hospital Quirónsalud Málaga

Málaga, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Universitario Lozano Blesa

Zaragoza, , Spain

Taichung Veterans General Hospital

Taichung, MA, Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Medical University Hospital

Taipei, , Taiwan

National Taiwan University Cancer Centre

Taipei, , Taiwan

National Taiwan University Hospital Hsin-Chu Branch

Zhubei, , Taiwan

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Newcastle upon Tyne Hospital (NHS)

Newcastle, , United Kingdom

Churchill Hospital - Oxford University Hospitals

Oxford, , United Kingdom

Countries

United States; Australia; France; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38853438 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38684230 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KisMET-01

Identifier Type: OTHER

Identifier Source: secondary_id

MYTX-011-01

Identifier Type: -

Identifier Source: org_study_id