Clinical trial NCT05652868: Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Keywords: cMET
MYTX-011
Mythic
MET
MYTX011
ADC
KisMET-01
Lead sponsor: Mythic Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-12-15
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.
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

Primary outcomes:
measure: Part 1: Number of patients with dose limiting toxicity (DLT)
timeFrame: Up to Day 21
measure: Part 2: Number of patients with tumor response
timeFrame: 2 years
Secondary outcomes:
measure: Part 1: Pharmacokinetic (PK) parameter (Total ADC)
timeFrame: 24 months
measure: Part 1: Pharmacokinetic (PK) parameter (Total antibody)
timeFrame: 24 months
measure: Part 1: Pharmacokinetic (PK) parameter (Free MMAE)
timeFrame: 24 months
measure: Part 1: ADA
timeFrame: 24 months
measure: Part 1: ORR
timeFrame: 24 months
measure: Part 1: DOR, TTR, DCR
timeFrame: 2 years
measure: Part 1: PFS
timeFrame: for up to 2 years after end of treatment
measure: Part 1: OS
timeFrame: for up to 2 years after end of treatment
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Adelaide
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Bordeaux
country: France
facility: Institut Bergonié-Bordeaux
city: Lyon
country: France
facility: Centre Léon Bérard - Lyon
city: Marseille
country: France
facility: APHM - Hopital de la Timone
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest (ICO institute)-St Herblain
city: Paris
country: France
facility: INSTITUT Curie (lead)
city: Toulouse
country: France
facility: Oncopole Claudius Regaud, IUCT-Oncopole
city: Villejuif
country: France
facility: Gustave Roussy Institute
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: MA
city: Busan
country: Korea, Republic of
facility: Kosin Univ. Gospel Hospital
city: Incheon
country: Korea, Republic of
facility: Chungbuk National Univ. Hospital
city: Seongnam
country: Korea, Republic of
facility: Gachon University
city: Seoul
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Suwon
country: Korea, Republic of
facility: St. Vincent Hospital
city: Barcelona
country: Spain
facility: Instituto Oncológico Dr Rosell (IOR) - Hospital Univ. Dexeus
city: Barcelona
country: Spain
facility: START Barcelona-HM CIOCC Early Phase Program
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: START Centro Integral Oncologico Calra Campal
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundación Jiménez Díaz
city: Malaga
country: Spain
facility: Hospital Quirónsalud Málaga
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Lozano Blesa
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
state: MA
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Cancer Centre
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Centre
city: Zhubei
country: Taiwan
facility: National Taiwan University Hospital Hsin-Chu Branch
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Newcastle upon Tyne Hospital (NHS)
city: Oxford
country: United Kingdom
facility: Churchill Hospital - Oxford University Hospitals
Study officials:
affiliation: Mythic Therapeutics
name: Ting Wu, MD MSc
role: STUDY_DIRECTOR
References: