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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05652868
• Other study ID #: MYTX-011-01
• Secondary ID: KisMET-01
• Status: Recruiting
• Phase: Phase 1
• Start date: March 23, 2023
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Mythic Therapeutics
• Contact: William T Downing
• Phone: 1-833-888-1138
• Email: clinicalsupport[@]mythictx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Cancer
• Advanced Non-Small Cell Squamous Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• NSCLC
• NSCLC Stage IIIB
• NSCLC Stage IV

Intervention

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

Locations

Country	Name	City	State
Australia	KisMET-01 Clinical Site	Adelaide	South Australia
Australia	KisMET-01 Clinical Site	Adelaide	South Australia
Australia	KisMET-01 Clinical Site	Blacktown	New South Wales
Australia	KisMET-01 Clinical Site	Camperdown	New South Wales
Korea, Republic of	MYTX-011-01 Clinical Site	Goyang
Korea, Republic of	KisMET-01 Clinical Site	Incheon
Korea, Republic of	KisMET-01 Clinical Site	Seoul
Korea, Republic of	KisMET-01 Clinical Site	Seoul
United Kingdom	KisMET-01 Clinical Site	Oxford
United States	KisMET-01 Clinical Site	Boston	Massachusetts
United States	KisMET-01 Clinical Site	Charleston	South Carolina
United States	KisMET-01 Clinical Site	Fairfax	Virginia
United States	KisMET-01 Clinical Site	Houston	Texas
United States	KisMET-01 Clinical Site	Milwaukee	Wisconsin
United States	KisMET-01 Clinical Site	Mineola	New York
United States	KisMET-01 Clinical Site	Morristown	New Jersey
United States	KisMET-01 Clinical Site	Nashville	Tennessee
United States	KisMET-01 Clinical Site	New York	New York
United States	KisMET-01 Clinical Site	Omaha	Nebraska
United States	KisMET-01 Clinical Site	Pittsburgh	Pennsylvania
United States	KisMET-01 Clinical Site	Rolling Meadows	Illinois
United States	KisMET-01 Clinical Site	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Mythic Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Part 1: Pharmacokinetic (PK) parameter (Total ADC)	Total ADC	24 months
Secondary	Part 1: Pharmacokinetic (PK) parameter (Total antibody)	Total antibody	24 months
Secondary	Part 1: Pharmacokinetic (PK) parameter (Free MMAE)	Free MMAE	24 months
Secondary	Part 1: ADA	Presence of anti-drug antibodies	24 months
Secondary	Part 1: ORR	Complete response + partial response	24 months
Secondary	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
Secondary	Part 1: PFS	Progression free survival	for up to 2 years after end of treatment
Secondary	Part 1: OS	Overall survival	for up to 2 years after end of treatment