A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Fadraciclib (CYC065), an Oral CDK2/9 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cyclacel Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Feb 2022 → 7 Jan 2025

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516289-12-00

EudraCT number

2021-002924-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Others, Efficacy, Dose response, Therapy, Pharmacodynamic, Pharmacokinetic

Phase 1:
To determine the maximum-tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of fadraciclib when administered orally twice daily (BID) or once daily (QD) in 28-day cycles in adult subjects with advanced solid tumors and lymphoma

Phase 2:
To evaluate preliminary efficacy of fadraciclib as measured by overall response rate (ORR) in subjects with locally advanced, recurrent, or metastatic, histologically confirmed advanced solid tumors or lymphoma who have failed all standard therapies or for whom standard therapy does not exist

Secondary objectives 1

1. Phase 1: - To assess safety and tolerability of fadraciclib - To investigate clinical pharmacokinetics (PK) of fadraciclib - To evaluate overall response rate (ORR) in subjects receiving fadraciclib Phase 2: - To assess the safety and tolerability of fadraciclib - To evaluate the disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS), in subjects receiving fadraciclib

Conditions and MedDRA coding

Endometrial cancer, Ovarian cancer, Biliary tract cancer, Hepatocellular carcinoma, B-cell lymphoma, T-cell lymphoma, Metastatic colorectal cancer, Breast cancer (metastatic HER-2 refractory, Hormone receptor +, HER-2 negative, and MBC post-CDK4/6 inhibitor, Triple-negative) Basket cohort: tumor types that are suspected to have a related mechanism of action and are not included in previous groups

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males or females aged ≥ 18 years or per local regulatory guidelines
2. Subjects with histological- or cytological-confirmed, advanced cancer who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists
3. ECOG performance status of 0 or 1
4. Subjects must have laboratory values as stated in the protocol
5. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days prior to starting the study drug. Both males and females must agree to use effective birth control during the study (prior to the first dose and for 6 months after the last dose) if conception is possible during this interval
6. Subjects must be able to swallow and retain orally administered medication and not have any clinically significant GI abnormalities that may alter the absorption, such as malabsorption syndrome or major resection of the stomach or bowels.
7. Able to agree to and sign the informed consent and to comply with the protocol.

Exclusion criteria 12

1. Subjects with a history of brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases. Subjects with treated brain metastases that are asymptomatic and have been clinically stable for at least 4 weeks will be eligible.
2. Subjects who have not received vaccines for SARS-COV-2 and have suspected signs and symptoms of COVID-19 or have confirmed COVID- 19.
3. Subjects with a history of another primary malignancy, please see additional details in the protocol.
4. Any other clinically significant acute or chronic medical or psychiatric condition or any laboratory abnormality that may increase the risk associated with study drug administration or may interfere with the interpretation of study results. See additional details in the protocol.
5. Diseases that significantly affect GI absorption of fadraciclib
6. Subjects who have impaired cardiac function or clinically significant cardiac disease, see additional details in the protocol.
7. Presence of active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment
8. Presence of an active infection requiring intravenous antibiotics
9. Presence of known history of human immunodeficiency virus-1/2 with uncontrolled viral load and on medications that may interfere with metabolism
10. Presence of active hepatitis B virus (HBV) or hepatitis C virus (HCV). In subjects with a history of HBV, hepatitis B core antibody testing is required and if positive, then HBV DNA testing will be performed, and if positive, the subject will be excluded. For subjects with HCV Ab positive, HCV viral load must be below the limit of quantification.
11. Chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 3 weeks (whichever is shorter) prior to administration of first dose of study drug on Day 1 or have not recovered from the side effects of such therapy. Patients on a stable dose os fulvestrant prior to enrollment may continue to receive fulvestrant.
12. Major surgery/surgical therapy for any cause within 4 weeks of the first dose

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 1: The incidence rate of dose-limiting toxicities (first cycle only) at each dose level. Phase 2: ORR according to Response Evaluation Criteria in Solid Tumors: RECIST guidelines (Lugano Criteria for lymphoma, mSWAT for CTCL) for each tumor type

Secondary endpoints 7

1. Safety
2. Disease control rate (DCR)
3. Response rate as per Lugano Criteria for lymphoma, mSWAT for CTCL
4. Progression-free survival
5. Duration of response
6. Overall survival
7. PK in Phase 1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cyclacel Limited

Sponsor organisation

Cyclacel Limited

Address

2 London Wall Place

City

London

Postcode

EC2Y 5AU

Country

United Kingdom

Scientific contact point

Organisation

Cyclacel Limited

Contact name

Khan Maola

Public contact point

Organisation

Cyclacel Limited

Contact name

Khan Maola

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications