Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer
- Conditions
- NSCLCNSCLC Stage IVNSCLC Stage IIIBNon-Small Cell Lung CancerAdvanced Non-Small Cell Squamous Lung CancerAdvanced Non-Small Cell Lung CancerAdvanced Non-Small Cell Non-Squamous Lung Cancer
- Interventions
- Registration Number
- NCT05652868
- Lead Sponsor
- Mythic Therapeutics
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
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
- Known to not have an actionable EGFR mutation. Subjects with or without other driver mutations are permitted to enroll.
- Must have received (or be ineligible for) available standard of care therapy.
- 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.
- 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.
- 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.
- 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.
- 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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Dose Escalation MYTX-011 Part 1 patients will receive MYTX-011. Part 2 Cohort A MYTX-011 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. Part 2 Cohort B MYTX-011 Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose. Part 2 Cohort C MYTX-011 Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose. Part 2 Cohort D MYTX-011 Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose. Part 2 Cohort E MYTX-011 Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose. Part 2 Cohort B2 MYTX-011 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 Part 2 Cohort E2 MYTX-011 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 Part 2 Cohort F MYTX-011 Part 2 Cohort F patients will receive MYTX-011 at the recommended phase 2 dose.
- Primary Outcome Measures
Name Time Method Part 1: Number of patients with dose limiting toxicity (DLT) Up to Day 21 The dose limiting toxicities will be based on number and severity of treatment-related adverse events.
Part 2: Number of patients with tumor response 2 years The overall response rate will be based on number of complete responses and partial responses.
- Secondary Outcome Measures
Name Time Method Part 1: OS for up to 2 years after end of treatment Overall survival
Part 1: Pharmacokinetic (PK) parameter (Total ADC) 24 months Total ADC
Part 1: Pharmacokinetic (PK) parameter (Total antibody) 24 months Total antibody
Part 1: Pharmacokinetic (PK) parameter (Free MMAE) 24 months Free MMAE
Part 1: ADA 24 months Presence of anti-drug antibodies
Part 1: ORR 24 months Complete response + partial response
Part 1: DOR, TTR, DCR 2 years Duration of response in patients that achieve CR or PR, time to response, best overall response and disease control rate
Part 1: PFS for up to 2 years after end of treatment Progression free survival
Trial Locations
- Locations (54)
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
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
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint 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
Kosin Univ. Gospel Hospital
🇰🇷Busan, Korea, Republic of
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, Korea, Republic of
Chungbuk National Univ. Hospital
🇰🇷Incheon, Korea, Republic of
Gachon University
🇰🇷Seongnam, Korea, Republic of
National Cancer Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
St. Vincent Hospital
🇰🇷Suwon, Korea, Republic of
Instituto Oncológico Dr Rosell (IOR) - Hospital Univ. Dexeus
🇪🇸Barcelona, Spain
START Barcelona-HM CIOCC Early Phase Program
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
START Centro Integral Oncologico Calra Campal
🇪🇸Madrid, Spain
START Madrid-FJD, Hospital Fundación Jiménez DÃaz
🇪🇸Madrid, Spain
Hospital Quirónsalud Málaga
🇪🇸Malaga, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Taichung Veterans General Hospital
🇨🇳Taichung City, MA, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
National Taiwan University Cancer Centre
🇨🇳Taipei, Taiwan
Taipei Medical University Hospital
🇨🇳Taipei City, 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