Clinical trial NCT05514132: A Study to Evaluate the Safety and Pharmacokinetics of Ceralasertib in Combination With Durvalumab in Chinese Patients With Advanced Solid Tumours
Official title: A Phase I, Multi-centre, Open-label, Dose Exploration Study to Assess the Safety and Tolerability of Ceralasertib in Combination With Durvalumab in Chinese Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumours
Keywords: Phase 1
Safety
Tolerability
Pharmacokinetics
Advanced solid tumours
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-08-24
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open-label study of ceralasertib given in combination with durvalumab in Chinese participants with advanced solid tumours. In each cohort, a monotherapy lead-in period (Cycle 0, duration of 7 or 14 days), prior to dosing with durvalumab, is added to investigate the PK profile and safety/tolerability of ceralasertib in Chinese participants.

This study is designed to investigate and characterise preliminary safety, tolerability, and PK of ceralasertib in DLT-evaluable Chinese participants

Detailed description: \<Objectives\>

Primary Objective:

To assess the safety and tolerability of ceralasertib in combination with durvalumab in Chinese patients with advanced solid tumours refractory/resistant to prior SoC therapy or for which no appropriate SoC therapy exists.

Secondary Objective:

To characterise the PK profile of ceralasertib after single- and multiple-doses administration. To characterise the anti-tumour activity and efficacy of ceralasertib in combination with durvalumab in Chinese patients .

\<Overall design\> This is a Phase 1, open-label study of ceralasertib given in combination with durvalumab in Chinese patients with advanced solid tumours.Results from this study will provide dose rationale for future investigations.

Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent.
2. At least 18 years of age at the time of signing the ICF.
3. Histological or cytological confirmation advanced solid tumour with refractory/resistance to a prior line of anti-PD-1/PD-L1-containing therapy (received as monotherapy or in combination) or for which no SoC exists.
4. Ability to swallow oral medication intact and retain it.
5. ECOG/WHO performance status of 0 to 1.
6. Must have a life expectancy of at least 12 weeks.
7. Participant must have had a treatment-free interval of ≥ 3 weeks from any prior therapy before the first dose of study treatment.
8. Body weight \> 35 kg and no cancer-associated cachexia (eg, CTCAE Grade 2 or worse weight loss over the 3 months prior to the Screening Visit).
9. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

1. Inadequate bone marrow reserve or organ function
2. As judged by the investigator, any evidence of uncontrolled intercurrent illness, that in the investigator's opinion makes it undesirable for the participant to participate in the study.
3. Spinal cord compression, leptomeningeal disease, or brain metastases, unless asymptomatic, treated, stable, and not requiring continuous corticosteroids
4. As judged by the investigator, any active disease or condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy
5. History of another primary malignancy.
6. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection including any patient known to have hepatitis B, hepatitis C, and HIV.
7. Known history of HIV infection.
8. Active cardiacvascular disease be consider as clinical significant.
9. Active or prior documented autoimmune or inflammatory disorders
10. Prior exposure to a CHK1 or ATR inhibitor.
11. As judged by the investigator, any unresolved treatment-related toxicities from previous anti-cancer therapy of CTCAE v5.0 Grade ≥ 2
12. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
13. Participants must not have experienced a toxicity that led to permanent discontinuation of prior anti-PD-1 or anti-PD-L1 immunotherapy.
14. Participants must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged
15. Participants with a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
17. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
18. Previous enrolment in the present study.
19. For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

Primary outcomes:
measure: The number of subjects with dose-limiting toxicity, as defined in the protocol.
timeFrame: From the first dose of study treatment Up to and including the end of cycle 1(each cycle is 28 days) .
measure: Safety and tolerability in terms of adverse events
timeFrame: From the first dose of study treatment until 28 days after the last dose.
Secondary outcomes:
measure: Plasma ceralasertib concentration(Cmax)
timeFrame: Cycle 0 Day1 to Day7, Cycle1 Day1 and Cycle 1 Day 7 or Day 8. At the end of Cycle1(each cycle is 28 days)
measure: Area under the plasma concentration versus time curve(AUC)
timeFrame: Cycle 0 Day1 to Day7, Cycle1 Day1 and Cycle1 Day7 or Day8. At the end of Cycle1(each cycle is 28 days)
measure: Overall response rate
timeFrame: At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28days) until objective disease progression as defined by RECIST version 1.1
measure: Duration of Response
timeFrame: At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28 days) until objective disease progression as defined by RECIST version 1.1
measure: Percentage Change in Tumour Size
timeFrame: At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28 days) until objective disease progression as defined by RECIST version 1.1
measure: Progression Free Survival
timeFrame: From start of treatment until the date of objective disease progression or death. (approximately 6 months).
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Jie Wang, PHD
role: PRINCIPAL_INVESTIGATOR
References: