A Phase 1 Study to Investigate Axatilimab Alone or in Combination With Durvalumab in Patients With Solid Tumors

Exclusion Criteria

• •1. Diagnosis of immunodeficiency or receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
• •a. Exceptions: 1) The use of physiologic doses of corticosteroids (i.e., ≤10 mg per day of equivalent prednisone) is allowed; 2) Steroids with no or minimal systemic effect (topical, inhalation) are allowed; 3) Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment; (4) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• •2. Previously treated with a CSF-1, CSF-1R, and/or IL-34-blocking agents
• •3. Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• •4. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the patient's best interest to participate, in the opinion of the treating Investigator, including, but not limited to:
• •1. Active or prior documented autoimmune or inflammatory disorders (see Appendix 3 for complete list).
• •2. History of active primary immunodeficiency
• •3. Known active or latent tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice).
• •4. Myocardial infarction or arterial thromboembolic events within 6 months prior to enrollment or severe or unstable angina, New York Heart Association (NYHA) (see Appendix 2) Class III or IV disease, or a QTc interval \> 470 msec. History of QTc prolongation, ventricular fibrillation, ventricular tachycardia or Torsades de Pointes (TdP).
• •5. Symptomatic congestive heart failure, cardiac arrhythmia, uncontrolled hypertension or diabetes mellitus.
• •6. Active infection requiring systemic therapy.
• •7. Interstitial lung disease
• •8. Serious chronic gastrointestinal conditions associated with diarrhea
• •9. Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (please see Appendix A (RECIST)) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its equivalent for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
• •5. Received a live attenuated vaccine within 30 days of the first dose of study drug.
• •Note: Patients, if enrolled, should not receive live vaccine whilst receiving study drug and up to 30 days after the last dose of study drug.
• •6. Administration of colony stimulating factors (including granulocyte-colony stimulating factor \[G-CSF\], granulocyte macrophage-colony stimulating factor \[GM-CSF\], or recombinant erythropoietin) within 4 weeks prior to the first dose of study drug treatment.
• •7. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• •8. Received chemotherapy, anti-cancer mAb, targeted small molecule or other systemic anti-cancer therapy within 4 weeks of the first dose of study drug. However, patients receiving conventional and investigational small molecule targeted therapies that are not expected to have delayed toxicities may enter the study 5 half-lives or 28 days after the last dose of the compound, whichever is shorter.
• •9. Currently receiving treatment with any other agent listed on the prohibited medication list.
• •10. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• •11. Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid \[qualitative\]). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• •12. Known alcohol or drug abuse.
• •13. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• •14. Legal incapacity or limited legal capacity.
• •15. Evidence of muscle disorders or muscle injury that are known to cause serum creatine kinase (CK) elevation
• •16. Current pneumonitis or has a history of (non-infectious) pneumonitis that required steroids
• •17. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• •18. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study drug. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• •19. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks or palliative radiation therapy within 2 weeks of the first dose of study drug
• •20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of study drug
• •21. History of allogenic organ transplantation.
• •22. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4.