A Study of the Safety, Pharmacokinetics and Exploratory Efficacy of RC220 in Combination with Osimertinib in Adult Patients with Non- Small Cell Lung Cancer.

Exclusion Criteria33

• Participation in a concurrent interventional trial.
• Persisting Grade 2 or higher severity AEs (except alopecia and neuropathy) from prior antitumour treatment, including as a result of maintenance osimertinib therapy, as per NCI-CTCAE v5.0.
• Females who are pregnant or lactating.
• Participants with bronchial (including atelectasis), mediastinal, pleural or vascular involvement.
• Have received cancer-directed therapy within the following timeframes:
• a. Antitumour therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy or investigational agent) within 28 days prior to the first dose of RC220 (or 5 times the half-life if shorter than 28 days), except for osimertinib.
• Note: exceptions may be considered on a case-by-case basis, as approved by the Sponsor Medical Monitor (MM) based on pharmacology.
• b. Wide-field radiation therapy within 28 days (or palliative radiation therapy within 7 days) prior to the first dose of RC220, or the participant has not recovered from the side effects of radiation therapy in the opinion of the Investigator.
• Note: Limited radiation to oligometastatic lesions (up to 3 at a time) is permitted.
• c. Any other concurrent investigational device(s), investigational agent(s) or conventional agent(s) within 28 days (unless 5 times the half-life is shorter than 28 days) prior to the first dose of RC220.
• d. Therapeutic radiopharmaceuticals must be stopped 8 weeks prior to the first dose of RC220.
• Persisting Grade 2 or higher severity AEs (except alopecia and neuropathy) from prior antitumour treatment, including as a result of maintenance osimertinib therapy, as per NCI-CTCAE v5.0.
• Participants with primary CNS malignancy, symptomatic CNS metastases, meningeal metastases, carcinomatous meningitis or leptomeningeal disease.
• Note: Participants with asymptomatic CNS metastases are eligible if clinically controlled.
• Had major surgery within 28 days of the screening visit. Exception: no waiting period applies following central venous catheter placement.
• History of tissue or organ transplantation.
• Treatment with systemic immunosuppressive or myelosuppressive medications within 4 weeks prior to the first dose of RC220 that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications. Exceptions: daily prednisone or
• equivalent less than or equal to 10 mg/day; topical, inhaled or intranasal corticosteroids.
• History of severe infection deemed clinically significant by the Investigator or designee within 4 weeks, or signs and symptoms of any active infection within 2 weeks prior to the first dose of RC220.
• Active hepatitis B or C. Note: Hepatitis B virus (HBV) carriers without active disease (HBV DNA titre < 1000 copies/mL or 200 IU/mL) or cured hepatitis C (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled.
• Confirmed human immunodeficiency virus (HIV) infection and receiving anti-retroviral therapy (ART). Participants with well controlled HIV infection (i.e., CD4+ count >350 cells per microlitre and viral copies less than 400/mL after at least 4 weeks of ART) may be eligible per discretion of the Investigator and with approval from Sponsor MM.
• Participants with any inherited predisposition to bleeding or to thrombosis (von Willebrand disease, haemophilia, etc.). Participants with a history of nontraumatic haemorrhage (i.e., end stage liver disease, any haemorrhage requiring medical intervention), thromboembolic event or any condition which may increase bleeding risk including clotting disorders, thrombocytopenia during the last 3 months prior to the first dose of RC220.
• Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgement of the Investigator might compromise the safety of the participant or integrity of the study, interfere with participation in the trial or compromise the trial objectives.
• Known allergies, hypersensitivity, or intolerance to the study drugs (RC220, osimertinib), or excipients.
• Any known, documented, or suspected history of illicit substance abuse that would preclude study participation. Exception: Physician-prescribed medicinal opioids or cannabinoids are allowed for pain management, at the discretion of the Investigator and
• in consultation with the Sponsor MM, as required.
• Vaccination with any live vaccine within 4 weeks prior to the first dose of study treatment.
• Use of new prescription or non-prescription medications, including complementary medicines, if the medication is a potential inhibitor of cytochrome P450 (CYP) isoform 3A4 and/or P-glycoprotein (P-gp), or if the medication is an inducer of CYP3A4 or P-gp,
• throughout study participation.
• Severe or uncontrolled cardiac disease requiring treatment, CHF (New York Heart Association) NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the 6 months prior to screening, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
• History of pneumonitis or interstitial lung disease.
• Judgement by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements.
• Psychological, familial, sociological, or geographical conditions that are likely to interfere with compliance to the protocol.