A Phase 1/2 Trial of CLN-081 in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer

JRCT ID: jRCT2041230017

Registered date:30/04/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Non-small cell lung cancer harboring EGFR exon 20 insertion mutations
• Date of first enrollment: 01/06/2023
• Target sample size: 20
• Countries of recruitment: United States,Japan,Hong Kong,Japan,Netherlands,Japan,Singapore,Japan,Taiwan,Japan,Spain,Japan,Italy,Japan,South Korea,Japan
• Study type: Interventional
• Intervention(s): CLN-081 is administered orally at a dose of 100 mg twice daily.

Outcome(s)

Primary Outcome

- ORR based upon independent central review by RECIST v1.1
- DOR based upon independent central review

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Histologically or cytologically confirmed locally advanced or metastatic NSCLC.
2. Documented EGFR ex20ins mutation demonstrated by a validated test and performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory. Institutions that don't have access to these tests should contact the sponsor for assistance.
3. Prior treatment in the recurrent/metastatic disease setting including:
a. A platinum-based chemotherapy regiment (or other chemotherapy regimen if platinum-based chemotherapy is contra-indicated)
b. Any other approved standard therapy that is available to the patient, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. In the case of a patient declining such therapy, documentation that the patient has been informed and declined should be documented in the medical record.
c. Prior therapy with an agent approved by the local regulatory authorities for the treatment of EGFR ex20ins mutant NSCLC (Module C only). (The agent approved by the local regulatory authorities is defined as an agent approved by one of the regulatory authorities.)
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
5. Age >= 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

Exclude criteria

1. Prior treatment with an EGFR ex20ins -targeting drug (eg, including, but not limited to poziotinib, mobocertinib, amivantamab, DZD9008, BDTX-189).
2. History of COVID-19-related pneumonitis requiring hospitalization.
3. History of COVID-19 infection within 4 weeks prior to enrolment, or clinically significant pulmonary symptoms related to prior COVID-19 pneumonitis.
4. Treatment with any of the following:
a. An EGFR TKI <= 8 days or 5 x the terminal phase t1/2, whichever is longer, prior to the first dose of study drug on C1D1.
b. Systemic anticancer treatment (excluding EGFR-TKIs as described above) within 14 days prior to the first dose of study drug on C1D1.
c. Immunotherapy <= 28 days prior to the first dose of study drug on C1D1.
d. Radiotherapy <= 28 days and palliative radiation <= 14 days prior to the first dose of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut progression prior to being eligible for evaluation as target lesions.
e. Major surgery (excluding placement of vascular access) <= 28 days of the first dose of study drug on C1D1.
5. Have any unresolved toxicity of Grade >= 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Patients with chronic but stable Grade 2 toxicities may be allowed to enrol after agreement between the Investigator and Sponsor.
6. Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, treated with surgery and/or radiation, and has been stable without requiring escalating corticosteroids or anti-convulsant medications for at least four weeks prior to the first dose of study drug on C1D1.
7. Prior therapy with CLN-081.
8. Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
9. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, treatment-related pneumonitis, or any evidence of clinically active interstitial lung disease.
10. Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
11. Resting QTc > 470 msec.
12. Patient is unable to take drugs po due to disorders or diseases that may affect GI function, including but not limited to inflammatory bowel diseases (eg, Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
13. Have any condition or illness that, in the opinion of the Investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
14. Pregnant, lactating women including if breastfeeding is interrupted or women who might be pregnant (including cases where a doctor's interview determines that the women may be pregnant); women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at within seven days prior to receiving study drug on C1D1. WOCBP and males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for six months following the last dose of study treatment (Female patients are not considered to be of childbearing potential if they are permanently sterile [hysterectomy, bilateral salpingectomy, or bilateral oophorectomy] or are post menopausal [no menses for 12 months without an alternative medical cause]).
15. History of another primary malignancy within 2 years prior to starting study drug on C1D1, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
16. Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including human immunodeficiency virus (HIV) and active clinical tuberculosis), or renal transplant; ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements.
17. For patients with a history of hepatitis B (HBV), active infection as defined by a positive hepatitis B serum antigen (HBsAg) test and detectable HBV deoxyribonucleic acid (DNA). Patients ineligible due to detectable levels of HBV DNA at baseline may be rescreened for enrolment if their HBV DNA levels become undetectable after treatment with antiviral agents, and upon agreement between the Investigator and Sponsor.
18. For patients with a history of hepatitis C, active infection as defined by a reactive hepatitis C virus (HCV) antibody test and detectable HCV ribonucleic acid (RNA).
19. Active bleeding disorders.

Related Information

• Primary Sponsor: Nasermoaddeli Ali
• Secondary Sponsor: Cullinan Therapeutics, Inc.
• Secondary ID(s): NCT04036682