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

Inclusion Criteria 1. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (all patients). 2. Documented EGFR ex20ins mutation demonstrated by a validated test listed in Section 9.7 and performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory (all patients other than Module A Food Effect PK Assessment Module). 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: 1. A platinum-based chemotherapy regiment (or other chemotherapy regimen if platinum-based chemotherapy is contra-indicated) 2. 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. 3. No prior therapy is required for patients enrolled on Module A. 4. Prior therapy with an agent approved by the local regulatory authorities for the treatment of EGFR ex20ins mutant NSCLC (Module C only). 4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (except for patients enrolled on Module A). 5. Age ≥ 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 7. Ability to take pills by mouth. 8. Have the following laboratory values: 1. Serum creatinine \< 1.5 × upper limit of normal (ULN) or calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (if calculated by Cockroft-Gault formula, the actual body weight must be used for CrCl unless body mass index \[BMI\] \>30 kg/m2 then lean body weight must be used). 2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome. 3. AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor. 4. Hemoglobin ≥ 9.0 g/dL in the absence of transfusion ≤ 14 days prior to the first dose of study drug on C1D1. 5. Platelets ≥ 100 × 109 cells/L in the absence of transfusion \<14 days prior to the first dose of study drug on Cycle 1 Day 1 (C1D1). 6. Absolute neutrophil count ≥ 1.5 ×109 cells/L. 9. For Module A patients only: patients must have a negative coronavirus disease 2019 (COVID-19) polymerase chain reaction test prior to enrolment. 10. For Module B and Module C patients only: verification of suitable archived tumor tissue available at the participating center for biomarker analysis. A fresh biopsy is required if an archived sample is not available. 11. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria R6, Phase 1 Expansion, Phase 2a, Module A and Module B Patients Only 1. Prior treatment with an EGFR ex20ins -targeting drug (eg, including, but not limited to poziotinib, mobocertinib, amivantamab, DZD9008, BDTX-189). Note: enrolment of patients treated previously with EGFR ex20ins-targeting drugs allowed selectively during accelerated titration dose escalation and Module C only. Module A Food Effect PK Assessment Module patients only 2. Conditions that compromise esophageal or gastrointestinal (GI) function, including esophageal, gastric, pancreatic, hepatobiliary, or small bowel carcinomas, or history of gastric resection. 3. Recurrent diarrhea, nausea, or vomiting. 4. Unable to refrain from or anticipates the use of: 1. Any drug, including prescription and non-prescription medications, including drugs that change gastrointestinal motility (eg, loperamide) or gastric pH (eg, antacids, H2 antagonists, proton pump inhibitors), herbal remedies, or vitamin supplements within 14 days prior to the first dosing on Day 1 to follow-up. 2. Any drugs known to be inhibitors or inducers of CYP3A enzymes and/or P-glycoprotein (P-gp), including St. John's Wort and grape fruit juice, within 28 days prior to the first dosing and throughout the PK assessment. 5. Any allergies to the composition of the high fat meal. 6. Patients who use tobacco products. All Patients 7. History of COVID-19-related pneumonitis requiring hospitalization. 8. History of COVID-19 infection within 4 weeks prior to enrolment, or clinically significant pulmonary symptoms related to prior COVID-19 pneumonitis. 9. Treatment with any of the following: 1. An EGFR TKI ≤ 8 days or 5 × the terminal phase t1/2, whichever is longer, prior to the first dose of study drug on C1D1. 2. Systemic anticancer treatment (excluding EGFR-TKIs as described above) within 14 days prior to the first dose of study drug on C1D1. 3. Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1. 4. 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. 5. Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1. 10. 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 enroll after agreement between the Investigator and Sponsor. 11. Have known or suspected leptomeningeal metastasis. Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, treated with surgery and/or radiation (if clinically indicated), 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. 12. Prior therapy with CLN-081. 13. Known hypersensitivity to CLN-081 or any drugs similar in structure or class. 14. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, treatment-related pneumo…

Reproduced word-for-word from the public registry record — the study team can answer questions about it.