A Modular, Phase I/II, Multicentre Study to Evaluate AZD4045, in Participants with Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• Inclusion Criteria:
• - Participant must be 18 years or older at the time of signing the informed consent form.
• - Participants must have documented diagnosis of MM according to the IMWG diagnostic criteria.
• - Participant must have one or more of the following measurable disease criteria:
• • Serum M-protein level ≥ 1.0 g/dL.
• • Urine M-protein ≥ 200 mg/24 h.
• • Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• - ECOG performance score of 0 to 1.
• - Participant must have screening bone marrow aspirate and/or archival sample adequate for clonal sequence calibration for MRD. An archival sample obtained from any time prior is acceptable.
• - Participant must have adequate organ and bone marrow function.
• - Participant must have received at least 3 prior classes of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• - Participant must have documented evidence of PD by IMWG 2016 criteria based on Investigator’s determination during or after the most recent line of therapy
• Exclusion Criteria:
• - Participant has a history of any grade IEC-HS and/or history of Grade ≥ 3 CRS and/or Grade ≥ 2 neurotoxicities during prior CAR-T cell therapy or T cell engaging therapy.
• - Participant has ongoing toxicity from previous anti-cancer therapy that did not resolve to baseline levels or to Grade ≤ 1 with the exception of alopecia or peripheral neuropathy.
• - Participant has a known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM.
• - Participant has systemic immunoglobulin light chain amyloidosis, active plasma cell leukaemia (presence of ≥ 5% of circulating plasma cells on a conventional peripheral blood smear) at time of screening, Waldenstrom macroglobulinemia or Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin (POEMS) syndrome.
• - Participant has a history of haematologic malignancies, other than MM, regardless of remission status.
• - Participant has a history of a prior non-haematologic malignancy unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years.
• - Participant has significant neurological or psychiatric condition (active or history of).
• - Participant is positive for any of the following:
• a) HIV (with exceptions)
• b) Chronic or active hepatitis B
• c) Active hepatitis C
• - Participant has clinically significant cardiovascular disease, including but not limited to:
• a) Myocardial infarction within 6 months prior to eligibility confirmation, or an
• unstable or uncontrolled disease/condition related to or affecting cardiac function.
• b) Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
• c) Congestive heart failure Class III or IV.
• d) Impaired cardiac function (LVEF < 45%).
• - Participant has any other significant medical condition which, in the opinion of the Investigator, places the participant at an unacceptable risk for treatment-related complications, could interfere with the successful or safe delivery of therapy, or could interfere with evaluation of study intervention or
• interpretation of participant safety or study results. These include but are not limited to:
• a) Serious active or uncontrolled infection.
• b) Requirement of supplemental oxygen to maintain oxygen saturation.
• c) Active autoimmune disease or a history of autoimmune disease within 2 years.
• d) Inflammatory bowel disease requiring treatment within the past 5 years or other clinically significant gastrointestinal condition.
• - Participant received live, attenuated vaccine within 28 days prior to eligibility
• confirmation
• - Participant has undergone major surgery within 28 days prior to eligibility confirmation
• - Concurrent enrolment in another clinical study (unless the study is observational, or the participant is in the follow-up period of an interventional study).
• - Participant has a known life-threatening allergy, hypersensitivity, intolerance, or a
• contraindication to any study intervention or their excipients.
• - Participant received any prior CAR-T or CAR-NK therapy directed at any target within 6 months prior to eligibility confirmation.
• - Participant received any prior TCE therapy directed at any target within 6 months prior to eligibility confirmation.
• - Participant received any prior BCMA-targeted treatment within 6 months prior to eligibility confirmation.
• - Participant with a history of refractoriness to the most recent BCMA-targeted treatment received as defined as PD on or within 60 days of last dose or non-responsiveness (ie, did not achieve at least minimal response) on therapy.
• - Participant received prior allogeneic stem cell transplant at any time.
• - Participant received autologous stem cell transplant within 3 months prior to eligibility confirmation.
• - Participant received radiation therapy for treatment of plasmacytoma within 14 days
• before eligibility confirmation.
• - Participant received prior anti-tumour therapy as follows prior to the first dose of lymphodepletion:
• a) Within 7 days:
• - Immunomodulatory or cereblon E3 ligase modulatory drugs.
• b) Within 14 days:
• - PI therapy.
• - Monoclonal antibody treatment for MM.
• - Cytotoxic therapy.
• - Other systemic anti-myeloma therapy.
• - Radiation.
• c) Within 14 days or at least 5 half-lives, whichever is longer:
• - Targeted therapy, epigenetic therapy, investigational drug or used an invasive investigational medical device.