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

Sponsor

Mythic Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05652868

Collaborator

(none)

150

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
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	Drug: MYTX-011	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Dose Escalation Part 1 patients will receive MYTX-011.	Drug: MYTX-011 MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.
Experimental: 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.	Drug: MYTX-011 MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.
Experimental: Part 2 Cohort B Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011 MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.
Experimental: Part 2 Cohort C Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011 MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.
Experimental: Part 2 Cohort D Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011 MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.
Experimental: Part 2 Cohort E Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose.	Drug: MYTX-011 MYTX-011 will be administered as an intravenous infusion every 21 days for up to two years.

Outcome Measures

Primary Outcome Measures

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

Part 1: Pharmacokinetic (PK) parameter [24 months]
Total ADC
Part 1: Pharmacokinetic (PK) parameter [24 months]
Total antibody
Part 1: Pharmacokinetic (PK) parameter [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
Part 1: OS [for up to 2 years after end of treatment]
Overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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