Study to Evaluate CCS1477 (Inobrodib) in Haematological Malignancies

Phase 1

Recruiting

• Conditions: Non Hodgkin Lymphoma; Haematological Malignancy; Acute Myeloid Leukemia; Higher-risk Myelodysplastic Syndrome; Multiple Myeloma; Peripheral T Cell Lymphoma
• Interventions: Drug: CCS1477; Drug: Pomalidomide; Drug: Azacitidine; Drug: Dexamethasone; Drug: Venetoclax

• Registration Number: NCT04068597
• Lead Sponsor: CellCentric Ltd.

Brief Summary

A Phase 1/2a study to assess the safety, tolerability, PK and biological activity of CCS1477 (inobrodib) in patients with Non-Hodgkin Lymphoma, Multiple Myeloma, Acute Myeloid Leukaemia or High Risk Myelodysplastic syndrome.

Detailed Description

This includes patients with Peripheral T-cell lymphoma.

Study Timeline

• Study Start: 2019-08-09
• Study First Submitted: 2019-08-12
• Study First Submitted QC: 2019-08-22
• Study First Posted: 2019-08-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-14
• Primary Completion: 2027-03-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Provision of consent
• ECOG performance status 0-2
• Patients with confirmed (per standard disease specific diagnostic criteria), relapsed or refractory haematological malignancies (NHL, MM and AML)
• Must have previously received standard therapy
• Adequate organ function

Exclusion Criteria

• Intervention with any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives of the first dose
• Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment
• Strong inhibitors of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
• Strong inducers of CYP3A4 within 4 weeks of the first dose of study treatment
• Patients should discontinue statins prior to starting study treatment
• CYP2C8 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
• Any unresolved reversible toxicities from prior therapy >CTCAE grade 1 at the time of starting study treatment (except alopecia and grade 2 neuropathy)
• Any evidence of severe or uncontrolled systemic diseases
• Any known uncontrolled inter-current illness
• QTcF prolongation (> 480 msec)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CCS1477 dose escalation NHL/MM	CCS1477	CCS1477 monotherapy
CCS1477 monotherapy expansion and combination dose finding and expansion - MM	CCS1477	CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone
CCS1477 monotherapy expansion and combination dose finding and expansion - AML	CCS1477	CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax
CCS1477 expansion phase NHL/Peripheral T-cell lymphoma	CCS1477	CCS1477 monotherapy
CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS	CCS1477	CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax
CCS1477 dose escalation AML/Higher risk MDS	CCS1477	CCS1477 monotherapy
CCS1477 monotherapy expansion and combination dose finding and expansion - MM	Pomalidomide	CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone
CCS1477 monotherapy expansion and combination dose finding and expansion - MM	Dexamethasone	CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone
CCS1477 monotherapy expansion and combination dose finding and expansion - AML	Venetoclax	CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax
CCS1477 monotherapy expansion and combination dose finding and expansion - AML	Azacitidine	CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax
CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS	Azacitidine	CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax
CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS	Venetoclax	CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-related adverse events	Up to 12 months	Treatment-related adverse events and serious adverse events
Incidence of laboratory abnormalities	Up to 12 months	Laboratory abnormalities characterised by type, frequency, severity and timing

Secondary Outcome Measures

Name	Time	Method
Duration of Response	Up to 12 months	Defined as the time from start of treatment until disease progression
Response rate	Up to 12 months	Defined as number of patients who have a response according to; * RECIL criteria (NHL); * IMWG criteria (Multiple myeloma); * ELN recommendations 2017 (AML)
AUC of CCS1477	35 days	Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration of CCS1477
Cmax of CCS1477	35 days	Maximum observed plasma concentration (Cmax) of CCS1477

Trial Locations

Locations (23)

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Community Health Network; 🇺🇸 Indianapolis, Indiana, United States

The Center for Cancer and Blood Disorders (CCBD); 🇺🇸 Bethesda, Maryland, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Penn Medicine - Abramson Cancer Center Perelman; 🇺🇸 Philadelphia, Pennsylvania, United States

University Hospital Vall D'Hebron; 🇪🇸 Barcelona, Spain

CIOCC Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

The Royal Marsden; 🇬🇧 Sutton, Surrey, United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust,; 🇬🇧 Bebington, United Kingdom

University Hospitals Bristol; 🇬🇧 Bristol, United Kingdom

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

Royal Derby Hospital; 🇬🇧 Derby, United Kingdom

Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Gartnavel General Hospital; 🇬🇧 Glasgow, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

Sarah Cannon Research Institute UK; 🇬🇧 London, United Kingdom

NIHR University College London Clinical Research Facility; 🇬🇧 London, United Kingdom

Imperial College; 🇬🇧 London, United Kingdom

The Christie Hospital; 🇬🇧 Manchester, United Kingdom

Newcastle upon Tyne Hospitals; 🇬🇧 Newcastle upon Tyne, United Kingdom

Cancer and Haematology Centre; 🇬🇧 Oxford, United Kingdom

University Hospital of Southampton; 🇬🇧 Southampton, United Kingdom