A non-randomised, single-arm, multi-centre, open-label Phase I/II trial to investigate novel cytokine release syndrome prevention in patients with multiple myeloma eligible to receive the bispecific T-cell engager antibody, teclistamab, within its licensed indication
Medical condition: relapsed or refractory multiple myeloma (RRMM) Medical condition in lay language: Myeloma (blood cancer) Therapeutic areas: Diseases [C] - Cancer [C04]
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 receiving teclistamab (Tecvayli). A total of approximately 30 evaluable patients will be enrolled. In the Phase I part of the study, an initial safety cohort of 6 patients will be enrolled and will receive POLB 001 at a dose of 150 mg twice daily (BID) for 14 days. Patients will be observed for Dose Limiting Toxicities (DLTs) over a 14-day period. If 2 or more patients encounter a DLT during this period, the safety cohort will be expanded by 3 patients, who will be observed at the same dose level for DLTs over a 14-day period. If 2 or more patients encounter DLT during this expansion period, a second safety cohort of 6 patients will be enrolled at a lower dose of 70mg BID and observed for DLTs for 14 days. Phase II part of the study starts when a dose is shown to be tolerable in the safety cohort (less than 2 pts with DLTs), and all the remainder of the planned patients can be enrolled at that dose level. To be evaluable for DLT assessment, a patient must receive at least 75% of the planned dose of POLB 001 and 2 doses of teclistamab in the initial 14-day evaluation period. Patients will receive POLB 001 twice daily for 14 days during Cycle 1 only, starting on D-4. Teclistamab will then be administered from D1 for 2 cycles. The treatment phase of the study will be followed by a 28-day safety follow-up period during which participants are allowed to receive teclistamab treatment to ensure a safe transition to local supply.
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.
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