INOBRODIB for Acute myeloid leukaemia | Higher-risk myelodysplastic syndrome | Multiple myeloma | Non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Written informed consent\n- Females must agree to use highly effective contraceptive measures (if sexually active), must not be breast feeding & must have a negative serum pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: •\tPost-menopausal defined as aged more than 50 years & amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. •\tDocumentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. •\tAmenorrhoeic for 12 months & serum follicle-stimulating hormone, luteinizing hormone & plasma oestradiol levels in the postmenopausal range for the institution. Note: All patients receiving pomalidomide or lenalidomide must fulfil the conditions of the Pregnancy Prevention Programme. Refer to the protocol for additional inclusion criteria for combination arms.\n- Willing&able to participate in all required evaluations and procedures\n- Men&women ≥18 years\n- ECOG performance status of ≤1 - for multiple myeloma patients in Part D3 and ECOG ≤ 2 for all other arms.\n- Patients with confirmed relapsed or refractory haematological malignancies (NHL, MM, AML & higher-risk MDS). Patients will include: •\tB-cell non-Hodgkin lymphoma - DLBCL, FL, MCL & Burkitt lymphoma •\tT-cell non-Hodgkin lymphoma •\tMultiple myeloma o Patients must have measurable disease by IMWG criteria defined as either serum M protein ≥0.5g/dL, or urine ≥200mg/24h, or involved SFLC ≥ 10mg/dL with abnormal FLC ratio •\tAML/secondary AML (patients with acute promyelocytic leukemia (APL) (FAB subtype M3) will be excluded) •\tHigher-risk MDS; according to revised IPSS-R\n- Must have received standard therapy. Must not require urgent cytoreductive therapy •\tNHL – patients must have exhausted or be ineligible for standard therapeutic options as available in the relevant geographical region; patient should not be eligible for hematopoietic stem cell transplantation; DLBCL patients should have received, or waiting for, CAR T cell treatment, if eligible and available; patients with indolent lymphomas must meet criteria for systemic therapy treatment. Patients should not be eligible for allogenic transplantation. •\tMM patients (except Parts D3), selected cohorts in D2; and D15-D18)) must have exhausted or be ineligible for standard therapeutic options as available in the relevant geographical region. For Parts D3 - (and selected small cohorts expansions in D2) MM patients must have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. •\tFor Parts D15-D18 – patients must be triple class exposed (a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody), and where treatment with elranatamb or teclistamab is recommended per local standard practice. •\tAML–relapsed or refractory following standard therapeutic options, including non-intensive therapy and targeted agents, as applicable considering disease and patient characteristics as well as availability of therapy in the relevant geographical region •\tHigher-risk MDS patients must have previously failed treatment with at least 4 cycles of a hypomethylating agent (if applicable).\n- Adequate haematologic function •\tAbsolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L) or ≥750 cells/mm3 in patients with Duffy null phenotype if this is considered their normal baseline •\tPlatelet count ≥75,000 cells/mm3 (75 x 109/L), screening result should be independent of platelet transfusion for at least 3 days. •\tHaemoglobin level ≥80 g/L. •\tFor further details on supportive medications see restrictions (Section 4.3.3) This criterion does not apply to AML/MDS patients. Patients with other malignancies involving bone marrow with parameters below the threshold may be considered eligible following discussion with the medical monitor •\tFor AML, WBC must be <10,000/μl\n- Adequate organ function at screening\n- Duration of the study & for 1 week after the last study medication administration (CCS1477 or combination agent), sexually active male patients must be willing to use barrier contraception i.e. condoms (with spermicide if locally approved for use) with all sexual partners. Where the sexual partner is a 'woman of child-bearing potential' who is not using effective contraception, men must use a condom (with spermicide if locally approved for use) & another form of contraception during the study & for 6 months after the last dose of study medication (CCS1477 or combination agent)"}

Exclusion criteria

• {"criterion_text":"- Treatment with any of the following: •\tAny investigational agent, chemotherapy, immunotherapy or anticancer agents from a previous clinical study within 14 days or 5 half-lives of first dose of study treatment. •\tStrong inducers of CYP3A4 taken within 4 weeks of the first dose of study treatment or whilst on study treatment •\tStrong inhibitors of CYP3A4 and or P-gp taken within 2 weeks of the first dose of study treatment or while on study treatment. The potent CYP3A4 inihibitor posaconazole is allowed in patients participating in the posaconazole DDI part of the study. Following review of the posaconazole DDI data, and with the agreement of the Safety Review Committee, concomitant use of posaconazole may be permitted thereafter in the study. •\tCYP3A4 and/or CYP2B6 and/or P-gp and/or OATP1B1 sensitive substrates and substates with narrow therapeutic index taken within 2 weeks of the first dose of study treatment & during Cycle 1. Note - Patients may receive pravastatin or fluvastatin (with monitoring for potential toxicities), or atorvastatin or simvastatin at 10mg daily dose only. •\tCYP2C8 sensitive and moderate substrates taken within 2 weeks of the first dose of study treatment and duryng Cycle 1. •\tHerbal medications taken within 7 days of the first dose of study treatment (4 weeks for St John's wort) or while on study treatment. •\tRadiotherapy with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks of the first dose of study treatment; palliative radiotherapy to ≤30% of the bone marrow within 2 weeks of the first dose of study treatment. •\tSteroids use >10mg daily (or 20mg daily for NHL) prednisolone or equivalent within 2 weeks of the first dose of study treatment. Replacement therapy steroids (even exceeding the above daily dose), given in the context of a transfusion, inhaled, nasal, topical and ophthalmic steroids are allowed. Note: For control of lymphoma related symptoms, patients may have received a brief (<7days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy. MM patients may receive >10mg daily if discussed and agreed with the medical monitor. •\tMedications with known risk of QT/QTc interval prolongation should be avoided concomitantly with CCS1477 unless essential in clinical management of the patient. If unavoidable, additional monitoring of potential QT/QTc interval prolongation is warranted •\tMajor surgery within 4 weeks of the first dose of study treatment. •\tShorter wash-out may be considered for some medications or palliative radiotherapy after discussion with medical monitor."}
• {"criterion_text":"- With the exception of alopecia, and CTCAE Grade 2 neuropathy, any unresolved toxicities from prior therapy > Grade 1 at the time of starting study treatment."}
• {"criterion_text":"- Active or unresolved spinal cord compression or CNS infiltration."}
• {"criterion_text":"- History of prior malignancy except for the following: •\tAdequately treated carcinoma in situ or non-melanomatous skin cancer •\tMalignancy treated with curative intent or in remission for >6 months after the last therapy may be eligible. Maintenance treatment is allowed. Note: Patients with a history of any haematological malignancy (other than indications included in the protocol) may be included following discussion with the medical monitor"}
• {"criterion_text":"- Any evidence of severe or uncontrolled systemic disease (e.g. current unstable or uncompensated respiratory or cardiac conditions; recent history of significant cardiac incidents, eg. significant cardiac dysfunction (congestive heart failure [NY Heart Association Class III or IV]; myocardial infarction within 12 months of starting study; unstable or poorly controlled angina pectoris) history of risk factors for torsades de pointes (e.g. heart failure, hypokalemia, family history of long QT syndrome or clinically significant arrhythmia; uncontrolled diabetes; history of, or active, bleeding diatheses; uncontrolled active systemic infection, including hepatitis B&C and human immunodeficiency virus (HIV), or active HBV, HCV, SARS-CoV2 (for patients receiving elranatamab or teclistamab) which in the investigator’s opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol."}
• {"criterion_text":"- Repeatable QTcF prolongation (>470 msec)."}
• {"criterion_text":"- History of severe allergic or anaphylactic reactions or any known severe allergies to any active or inactive ingredients in the study medications (CCS1477 and/or pomalidomide, lenalidomide,dexamethasone, isatuximab, ixazomib, bortezomib, elranatamab, teclistamab, posaconazole, azacitidine or venetoclax as applicable)."}
• {"criterion_text":"- Female patients who are pregnant or breast-feeding at any time during the study."}
• {"criterion_text":"- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. Refer the protocol for additional exclusion criteria for combination arms."}

Primary endpoints

• {"endpoint_text":"- The primary outcome measure for the study is: Safety and tolerability of CCS1477 as monotherapy and in combination.\n- Safety and tolerability will be assessed in terms of AEs, laboratory data, vital signs and ECG changes. These will be collected for all patients. Appropriate summaries of these data will be presented.","definition_or_measurement_approach":"Safety and tolerability assessed by collection and summarisation of adverse events (AEs), laboratory data, vital signs and ECG changes for all patients."}

Secondary endpoints

• {"endpoint_text":"- To characterise the pharmacokinetics (PK) of CCS1477, following a single dose and at steady state after multiple dosing as monotherapy and in combination.\n- To assess preliminary tumour response/activity of CCS1477 in patients with relapsed or refractory haem. malignancies (NHL, MM and AML/higher-risk MDS).\n- Anti-tumour activity defined by measurement of changes in: - NHL - Radiological assessment, bone marrow disease status and serum immunoglobulins and Tumour biopsy. -MM - Blood/urine samples for myeloma response, bone/bone marrow disease status and serum immunoglobulins. -AML and MDS - Bone marrow disease status.\n- To obtain a preliminary assessment of CCS1477 by evaluation of overall survival (OS).","definition_or_measurement_approach":"PK: Characterise CCS1477 PK after single dose and at steady state after multiple dosing (monotherapy and combination). Tumour response/activity: assessment by radiological assessment, bone marrow disease status, serum immunoglobulins, tumour biopsy (for NHL); blood/urine myeloma response measures, bone/bone marrow status, serum immunoglobulins (for MM); bone marrow disease status (for AML/MDS). Overall survival measured as OS."}

Spain

Earliest CTIS Part Ii Submission Date

04-04-2025

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

346

Number Of Sites

11

Number Of Participants

16

Primary sponsor

Full Name

Cellcentric Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Iqvia Biotech Limited

Responsibilities

Sponsor duties codes: 13

Name

spm²-safety projects & more GmbH

Responsibilities

SAE processing, DSUR writing and submission to authorities, Signal Management Quarterly reviews; sponsor duties code: 8

Name

Pivotal S.L.

Responsibilities

Sponsor duties codes: 1,12,2,5

Name

European Packaging Centre B.V.

Responsibilities

Sponsor duties code: 14

Name

Almac Clinical Services Limited

Responsibilities

Sponsor duties code: 14

Name

Alderley Analytical Limited

Responsibilities

Sponsor duties code: 4

Name

Colibri Scientific Limited

Responsibilities

Sponsor duties code: 4

Name

Veristat LLC

Responsibilities

Sponsor duties codes: 6,7

Third parties

• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"codes: 13","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"spm²-safety projects & more GmbH","duties_or_roles":"codes: 15 (SAE processing, Development Safety Update Reports (DSUR) writing and submission to authorities, Signal Management Quarterly reviews); 8","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"codes: 1, 12, 2, 5","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"European Packaging Centre B.V.","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Alderley Analytical Limited","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Colibri Scientific Limited","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veristat LLC","duties_or_roles":"codes: 6, 7","organisation_type":"Pharmaceutical company"}