Medical condition: relapsed or refractory multiple myeloma (RRMM) Medical condition in lay language: Myeloma (blood cancer) Therapeutic areas: Diseases [C] - Cancer [C04] Cancer
Conditions
Interventions
This is a non-randomised, single-arm study seeking to evaluate the safety and early efficacy signals of POLB 001, a novel oral small molecule inhibitor of Cytokine Release Syndrome (CRS), in patients
Sponsors
DIDACT Foundation
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Male or female participants aged =18 years at the time of informed consent. 2. Participants must be able to give signed informed consent and be willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 3. Participant must be able to take oral medication. 4. Prior diagnosis of MM as defined according to IMWG criteria 5. Patients must fulfil NICE criteria for teclistamab eligibility via the NHS; 5.1. Prior diagnosis of relapsed or refractory multiple myeloma (RRMM) 5.2. Received at least three prior treatment therapies for RRMM, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody 5.3. Documented evidence of progressive disease based on investigator’s determination of response by IMWG criteria on or after their last regimen. 6. ECOG performance status =2. 7. Adequate hepatic function characterized by the following: Total bilirubin =2 x ULN (=3 x ULN if documented Gilbert’s syndrome); AST =2.5 x ULN; and ALT =2.5 x ULN 8. Adequate renal function defined by an estimated creatinine clearance =30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method). 9. Adequate BM function characterized by the following: 9.1. ANC =1.0 × 109/L (use of granulocyte-colony stimulating factors is permitted if completed at least 7 days prior to planned start of dosing); 9.2. Platelets =25 × 109/L (transfusion support is permitted if completed at least 7 days prior to planned start of dosing); 9.3. Haemoglobin =8 g/dL (EPO and transfusion support is permitted). 10. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade =1.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with an anti-BCMA bispecific antibody 2. Active plasma cell leukaemia 3. Amyloidosis 4. POEMS syndrome 5. Prior antitumor therapy as follows, in the specified time frame prior to the first dose of study treatment: 5.1. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. 5.2. Gene-modified adoptive cell therapy (eg, CAR-modified T-cells, NK cells) within 3 months. 5.3. mAb treatment or bispecific T-cell redirector therapy for multiple myeloma within 21 days. 5.4. Cytotoxic therapy within 14 days. 5.5. PI therapy within 14 days. 5.6. Immunomodulatory agent therapy within 7 days. 5.7. Radiotherapy within 14 days. However, if palliative focal radiation is used, the participant is eligible irrespective of the end date of radiotherapy. 6. Stem cell transplant: 6.1. An allogeneic stem cell transplant within 6 months before enrolment. Participants who received an allogeneic transplant must be off all immunosuppressive medications for =42 days without signs of graft versus host disease before enrolment. 6.2. An autologous stem cell transplant within 12 weeks before enrolment. 7. Impaired cardiovascular function [ NYHA stage III OR IV] or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrolment 8. QTcF over 480ms at screening 9. Ongoing Grade =2 peripheral sensory or motor neuropathy. 10. Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 7 days prior to enrolment. 11. Other ongoing active malignancies within 1 year except carcinoma in situ or BCC/SCC that has been adequately treated 12. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients 13. Received a cumulative dose of corticosteroids equivalent to =140 mg of prednisone within 14 days before enrolment. 14. CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole-brain MRI and lumbar cytology are required. 15. Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is shorter). 16. Live attenuated vaccine must not be administered within 4 weeks of the first dose of study intervention. Non-live or non-replicating vaccines authorized for emergency use (eg, COVID-19) by local health authorities are allowed. 17. Participant had major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment. 18. Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study 19. Female patients must not be pregnant or breastfeeding; 19.1. Females of childbearing potential must be willing to use a highly effective method of contraception (hormonal birth control; abstinence). 19.2. A female participant of childbearing potential must have a negative highly s
Countries
England, United Kingdom
Contacts
Public Contact- Study Management
Outcome results
None listed