Autologous Chimeric Antigen Receptor (CAR) T-cells Targeting the Kappa Myeloma Antigen (KMA) in Kappa Restricted Multiple Myeloma Patients With Relapsed/Refractory Disease

Inclusion Criteria: 1. Patient has provided written informed consent using the KOALA Patient Information and Consent Form (PICF) 2. Age ≥ 18 years on the day of signing informed consent form 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2 (Appendix 2) 4. Life expectancy of ≥ 3 months, as assessed by the Investigator 5. A diagnosis of kappa-restricted RR MM with evidence of KMA on the surface of bone marrow plasma cells using flow cytometry analysis as determined by investigator 6. Have received at least 2 prior lines of therapy including a proteosome inhibitor and an immunomodulatory imide drug with evidence of disease progression as per IMWG criteria (Appendix 1) after the most recent line of therapy Note 1: induction with or without haematopoietic stem cell transplant (SCT), consolidation and maintenance therapy is considered a single line of therapy Note 2: Patients who have had prior treatment with a CAR T-cell therapy are eligible after a minimum of a 12 week washout between infusions. 7. Have measurable disease as defined by: • Serum IgG, IgA, IgM M protein ≥ 0.5 g/dL; or • Serum IgD M protein ≥ 0.05 g/dL; or • An abnormal free light chain (FLC) assay (Freelite™) demonstrating an excess of kFLC with a kFLC component of at least 100 mg/L and an abnormal k:λ FLC ratio Note: Patients who do not have measurable disease but who have demonstrable disease (i.e., oligo-secretory myeloma) based on evidence of bone lesions by at least 2 prior PET scan studies showing persistent disease may be included 8. Last dose of nitrosourea, nitrogen mustards, or monoclonal antibody must have been at least 4 weeks prior to registration; autologous SCT must have been at least 12 weeks prior to registration; and allogeneic SCT must have been at least 24 weeks prior to registration. Limited field radiotherapy to painful lesions is allowed during Screening and bridging but must be completed 48 hours prior to planned apheresis and lymphodepleting chemotherapy 9. Adequate haematological function documented within 7 days prior to registration, defined as: • Haemoglobin ≥ 80 g/L (peripheral red blood cell transfusion support is allowed if marrow infiltrate is ≥ 50%) • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (GCSF support is allowed) , and ANC \> 0.5 x 109/L is allowed if neutropenia is due to disease infiltration of bone marrow) • Absolute lymphocyte count (ALC) ≥ 0.1 x 109/L • Platelets ≥ 50 x 109/L (platelet transfusion support is allowed for platelets ≥ 30 if due to disease infiltration by bone marrow, or splenomegaly due to disease involvement) 10. Adequate cardiac function, defined as: • Left ventricular ejection fraction (LVEF) ≥ 40% on echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 90 days prior to registration• No suspicion for intercurrent deterioration in left ventricular function as assessed by the Investigator 11. Adequate pulmonary function, defined as: • Oxygen saturation measured by pulse oximetry ≥ 90% on room air 12. Adequate renal function documented within 7 days prior to registration, defined as any one of: • A serum creatinine ≤ 1.5 x upper limit of normal (ULN) • Creatinine clearance (CrCl) of ≥ 40 mL/min calculated by Cockcroft-Gault formula (Appendix 3) • CrCl ≥ 40 mL/min calculated by 24-hour urine collection post-ovulation methods) and withdrawal are not acceptable • Glomerular filtration rate (GFR) ≥ 40 mL/min by renal scintigraphy 13. Adequate hepatic function documented within 7 days prior to registration, defined as all of: • Total bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN in patients with Gilbert's syndrome or documented liver involvement) • Alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in patients with documented liver involvement) • Aspartate aminotransferase (AST) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in patients with documented liver involvement) 14. Taking a maximum corticosteroid dose of 20 mg of oral prednisone or equivalent 15. Females of childbearing potential (FCBP) and nonsterile male patients (with partners of childbearing potential) must agree to use highly effective methods of contraception from registration on the study to 2 months after the PMCC-COE-KMA infusion or until PMCC-COE-KMA CAR T-cells are no longer present by quantitative PCR on 2 consecutive tests whichever is later. Effective methods of contraception are: • Total abstinence from sexual intercourse when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptablemethods of contraception • Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least 6 weeks prior to registration. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by followup hormone level assessment • Male sterilisation (at least 6 months prior to Screening), noting that for female patients on the study, the vasectomised male partner should be the sole partner for that patient • Use of oral, (oestrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months prior to registration • Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., ageappropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks prior to registration. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential 16. Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test within 3 days prior to registration 17. Sexually active male patients must use a condom during intercourse and must agree to refrain from sperm donation, from registration on the study until 52 weeks after the PMCC-COE-KMA infusion Exclusion Criteria: 1. A diagnosis of lambda-restricted MM 2. Plasma cell leukaemia at the time of Screening (\> 5% circulating plasma cells by standard differential), Waldenström's macroglobulinaemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis 3. Known active, or prior history of, central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM 4. Major surgery within 4 weeks prior to registration 5. Receipt of a live, attenuated vaccine (except for COVID-19) within 4 weeks prior to the planned commencement of lymphodepleting conditioning 6. Receipt of any investigational medical product within the last 30 days, or after 5 halflives (whichever is the shortest) prior to planned leukapheresis 7. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months prior to Screening or class III to IV cardiac disease as defined by the New York Heart Association Functional Classification 8. Clinically significant neurological disorders (e.g., uncontrolled seizure disorder, severe brain injury, dementia, Parkinson's disease, or autoimmune/inflammatory disorders \[e.g., Guillain-Barre syndrome, motor neuron disease, chronic inflammatory demyelinating polyneuropathy\]) Note: Patients with a seizure disorder who have been seizure free and without modification to anti-epileptic therapy in the past 12 months are eligible 9. History of other active malignancy, with the exception of: • Adequately treated in situ carcinoma of the cervix or breast • Adequately treated basal cell carcinoma of skin or localised squamous cell carcinoma of the skin • Low grade malignancies that are being observed and do not require treatment (e.g., low risk prostate cancer) • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and without evidence of recurrence for at least 2 years prior to registration 10. Active human immunodeficiency virus (HIV) or hepatitis A, B, or C infection • Patients who are positive for HIV by enzyme-linked immunosorbent assay or Western Blot, are ineligible • Patients who are seropositive for hepatitis C virus (HCV) are eligible if their most recent HCV DNA assay is undetectable (including those that have received curative therapy) • Patients who are seropositive for hepatitis B virus (HBV) because of vaccination are eligible 11. Other clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, viral DNA/RNA by PCR) 12. A known history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy (with the exception of corticosteroids up to 20 mg/day of oral prednisolone or equivalent) 13. Current active graft-versus-host disease requiring immunosuppression (with the exception of corticosteroids up to 20 mg/day of oral prednisolone or equivalent) 14. Other significant life-threatening illness, medical condition, or laboratory abnormality that, in the opinion of the Investigator, could compromise the patient's safety, impair their ability to receive PMCC-COE-KMA, or put the study outcomes at undue risk 15. Known hypersensitivity to the excipients of PMCC-COE-KMA or to any product to be given to the patient as per the study protocol (e.g., tocilizumab and lymphodepleting agents) 16. Women who are lactating 17. Presence of any psychological, social, geographical, or other condition for which, in the opinion of the site Investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments