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

• ClinicalTrials.gov Identifier: NCT05652868
• Recruitment Status: Recruiting
• First Posted: December 15, 2022
• Last Update Posted: April 3, 2024
• Sponsor: Mythic Therapeutics
• Information provided by (Responsible Party): Mythic Therapeutics

Tracking Information

• First Submitted Date: November 29, 2022
• First Posted Date: December 15, 2022
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: March 23, 2023
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2022)

• Part 1: Number of patients with dose limiting toxicity (DLT) [ Time Frame: 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 [ Time Frame: 2 years ]
  The overall response rate will be based on number of complete responses and partial responses.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 1, 2024)

• Part 1: Pharmacokinetic (PK) parameter (Total ADC) [ Time Frame: 24 months ]
  Total ADC
• Part 1: Pharmacokinetic (PK) parameter (Total antibody) [ Time Frame: 24 months ]
  Total antibody
• Part 1: Pharmacokinetic (PK) parameter (Free MMAE) [ Time Frame: 24 months ]
  Free MMAE
• Part 1: ADA [ Time Frame: 24 months ]
  Presence of anti-drug antibodies
• Part 1: ORR [ Time Frame: 24 months ]
  Complete response + partial response
• Part 1: DOR, TTR, DCR [ Time Frame: 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 [ Time Frame: for up to 2 years after end of treatment ]
  Progression free survival
• Part 1: OS [ Time Frame: for up to 2 years after end of treatment ]
  Overall survival

Original Secondary Outcome Measures (submitted: December 7, 2022)

• Part 1: Pharmacokinetic (PK) parameter [ Time Frame: 24 months ]
  Total ADC
• Part 1: Pharmacokinetic (PK) parameter [ Time Frame: 24 months ]
  Total antibody
• Part 1: Pharmacokinetic (PK) parameter [ Time Frame: 24 months ]
  Free MMAE
• Part 1: ADA [ Time Frame: 24 months ]
  Presence of anti-drug antibodies
• Part 1: ORR [ Time Frame: 24 months ]
  Complete response + partial response
• Part 1: DOR, TTR, DCR [ Time Frame: 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 [ Time Frame: for up to 2 years after end of treatment ]
  Progression free survival
• Part 1: OS [ Time Frame: for up to 2 years after end of treatment ]
  Overall survival

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

Drug: MYTX-011

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

Study Arms

• Experimental: Part 1 Dose Escalation
  Part 1 patients will receive MYTX-011.
  Intervention: Drug: MYTX-011
• 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.
  Intervention: Drug: MYTX-011
• Experimental: Part 2 Cohort B
  Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose.
  Intervention: Drug: MYTX-011
• Experimental: Part 2 Cohort C
  Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose.
  Intervention: Drug: MYTX-011
• Experimental: Part 2 Cohort D
  Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose.
  Intervention: Drug: MYTX-011
• Experimental: Part 2 Cohort E
  Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose.
  Intervention: Drug: MYTX-011

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2022): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2027
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

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:

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: William T Downing; 1-833-888-1138; clinicalsupport@mythictx.com

Contact: Lisa Haystrand, MSc; 1-833-888-1138; clinicalsupport@mythictx.com

• Listed Location Countries: Australia, Korea, Republic of, United Kingdom, United States

Administrative Information

• NCT Number: NCT05652868
• Other Study ID Numbers: MYTX-011-01; KisMET-01 ( Other Identifier: Mythic Therapeutics )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: At the conclusion of the study

• Current Responsible Party: Mythic Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Mythic Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ting Wu, MD MSc; Mythic Therapeutics

• PRS Account: Mythic Therapeutics
• Verification Date: April 2024