A Phase 1 Multicenter Dose Escalation and Dose Expansion Study of the study drug MYTX-011 in Subjects with Non-Small Cell Lung Cancer Cell Lung Cancer – KisMET-01
- Conditions
- on-Small Cell Lung CancerCancer
- Registration Number
- ISRCTN57038506
- Lead Sponsor
- Mythic Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 200
Subjects must meet all the following inclusion criteria to be eligible for participation in this study:
1. Part 1:
a. Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC and have received available standard of care therapy.
b. There is no limit on the number of prior therapies that can have been received.
2. Part 2 (Cohorts A-E):
a. Known to not have an actionable EGFR mutation. Subjects with or without other driver mutations are permitted to enroll.
b. Must have received available standard of care therapy.
c. Must have progressed on at least 1 line of prior therapy in the locally advanced/metastatic setting. Note: multiple lines of tyrosine kinase inhibitor (TKI) for the same actionable mutation count as 1 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.
d. 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).
e. 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.
f. Subjects with actionable gene alterations (other than EGFR) 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 alternation 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).
3. Part 2:
a. Cohort A:
i. Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC.
ii. Tumor sample with high cMET expression by IHC (3+ with tumor cell positivity of =50%) confirmed by central laboratory testing.
b. Cohort B:
i. Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC.
ii. Tumor sample with intermediate cMET expression by IHC (3+ with tumor cell positivity of = 25% - <50%) confirmed by central laboratory testing.
c. Cohort C:
i. Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic squamous NSCLC.
ii. Tumor sample with cMET overexpression by IHC (2+ with tumor cell positivity of = 25%) confirmed by central laboratory testing.
d. Cohort D:
i. Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC.
ii. Tumor sample that does not meet cMET IHC entry criteria for Cohorts A and B (for subjects with non-squamous NSCLC) and C (for subjects with squamous
NSCLC) based on central laboratory testing.
iii. Known MET amplification or exon 14 skipping mutations, respectively, performed in a CLIA-certified laboratory in the US or equivalently accredited diagnostic labo
Subjects who meet any of the following exclusion criteria will be excluded from this study:
1. NSCLC with adeno-squamous histology (for Cohorts A, B, and C only; subjects with NSCLC with adeno-squamous histology are allowed in Cohorts D and E).
2. Radiation to the lung within 6 weeks prior to screening. For all other sites (except lung and brain), therapeutic or palliative radiation within 2 weeks of the first dose of study drug. Must have recovered from all radiation-related toxicity.
3. Major surgery within 28 days before first dose of study drug administration.
4. Systemic anticancer therapy including investigational drugs, within the lesser of 28 days or 5 half-lives of the prior therapy before starting study drug (14 days or 5 half-lives for small molecule targeted therapy).
Concurrent use of hormonal therapy for breast cancer or prostate cancer is permitted.
5. Previously received cMET-targeted antibody or ADC, bicycle, or small peptide therapies targeting cMET.
Note: For Cohort E: Subjects will have previously received and progressed on either cMET-targeted ADC or antibody; however, they must not have been intolerant to the
cMET-targeted ADC or antibody therapy.
6. Use of any concomitant or prohibited therapies outlined in Section 7.6.
7. Untreated, uncontrolled CNS metastases. Subjects with CNS metastases who have had surgical resection or have received radiation therapy to all known sites of CNS disease ending at least 4 weeks prior to first dose of study drug are eligible if:
a. There is no evidence of disease progression after at least 2 weeks after the end of definitive therapy; and
b. The subject is neurologically stable and either off or on a non-increasing dose (in the past 2 weeks) of systemic steroids.
8. Known history of human immunodeficiency virus (HIV) infection.
9. Untreated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
a. HBV: Subjects with serological evidence of chronic HBV infection should have an HBV viral load below the limit of quantification to be eligible. In addition, subjects
with positive HBsAg should be on anti-HBV therapy at enrollment and while receiving MYTX-011.
b. HCV: Subjects with history of HCV infection should have completed curative antiviral treatment and have HCV viral load below the limit of quantification.
10. Myocardial infarction, unstable angina, PTCA or CABG or cerebrovascular event (stroke or transient ischemic attack [TIA]) within 6 months before first dose of study drug, symptomatic congestive heart failure (New York Heart Association [NYHA] > Class II; see Appendix B), or ventricular arrhythmias requiring treatment.
11. Elevated corrected QT interval (QTc) >480 ms based on Fridericia’s correction formula.
12. 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.
13. Subject requires systemic steroid therapy: prednisone 10 mg daily or equivalent. Inhaled steroids or topical steroid use is permitted.
14. Clinically significant systemic illness that could pose undue risk to the subject or confound the ability to interpret study results.
15. Active infection requiring IV antibiotics, antivirals, or antifungal medication within 14 days of Cycle 1 Day 1.
16. Neuropathy > Grade 1 for any reason.
17. History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part 1: MYTX-011 Dose Escalation<br> 1. Incidence and severity of TEAEs, AEs, and clinically significant changes from baseline in vital signs, ECGs, and<br>laboratory parameters<br>2. The RP2D will be selected as a biologically active dose at or below the MTD (or the highest dose tested if the<br>3. MTD is not identified during the study) MTD will be determined by DLTs during Cycle 1. The observation period for DLTs is Cycle 1.<br><br>Part 2: MYTX-011 Dose Expansion (Cohorts A-E)<br>1. ORR (confirmed CR+PR) in each expansion cohort according to RECIST 1.1 at Screening, Cycles 2 and 4 at day 1, Cycle 5 for 2 years, End of Trial, Long Term Survival Follow-up.
- Secondary Outcome Measures
Name Time Method