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

Mythic Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Non-Small Cell Squamous Lung Cancer; NSCLC Stage IV; Advanced Non-Small Cell Non-Squamous Lung Cancer; Advanced Non-Small Cell Lung Cancer; NSCLC Stage IIIB; Non-Small Cell Lung Cancer; NSCLC

Treatments: Drug: MYTX-011

Study type: Interventional

Funder types: Industry

Identifiers

NCT05652868

KisMET-01 (Other Identifier)

MYTX-011-01

Details and patient eligibility

About

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).

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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150 participants in 6 patient groups

Part 1 Dose Escalation

Experimental group

Description:

Part 1 patients will receive MYTX-011.

Treatment:

Drug: MYTX-011

Part 2 Cohort A

Experimental group

Description:

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.

Treatment:

Drug: MYTX-011

Part 2 Cohort B

Experimental group

Description:

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

Treatment:

Drug: MYTX-011

Part 2 Cohort C

Experimental group

Description:

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

Treatment:

Drug: MYTX-011

Part 2 Cohort D

Experimental group

Description:

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

Treatment:

Drug: MYTX-011

Part 2 Cohort E

Experimental group

Description:

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

Treatment:

Drug: MYTX-011