SUMIT-ELA: A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer

Sponsor

Carrick Therapeutics Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05963997

Collaborator

Berlin-Chemie AG Menarini Group (Industry)

Enrollment

Locations

Arms

22.6

Anticipated Duration (Months)

1.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer Locally Advanced Breast Cancer Breast Cancer	Drug: Samuraciclib Drug: Elacestrant Dihydrochloride	Phase 1/Phase 2

Detailed Description

This is a multiple cohort study, an initial dose escalation phase is designed to confirm the safe dose of samuraciclib in combination with elacestrant. A Safety Review Committee (SRC) will monitor the safety, tolerability, and PK data during this phase. Once ascertained, an expansion cohort will be opened to explore the efficacy of samuraciclib in combination with elacestrant.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2 Open-label Study of Samuraciclib in Combination With Elacestrant in Participants With Metastatic or Locally Advanced Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2-negative Breast Cancer

Anticipated Study Start Date :

Jul 30, 2023

Anticipated Primary Completion Date :

Dec 23, 2024

Anticipated Study Completion Date :

Jun 16, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Up to 6 evaluable participants will receive samuraciclib 240 mg in combination with elacestrant 300 mg in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards).	Drug: Samuraciclib Samuraciclib capsules by mouth once a day Drug: Elacestrant Dihydrochloride Elacestrant tablets by mouth once a day Other Names: ORSERDU
Experimental: Cohort 2 Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 300 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).	Drug: Samuraciclib Samuraciclib capsules by mouth once a day Drug: Elacestrant Dihydrochloride Elacestrant tablets by mouth once a day Other Names: ORSERDU
Experimental: Cohort 3 Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).	Drug: Samuraciclib Samuraciclib capsules by mouth once a day Drug: Elacestrant Dihydrochloride Elacestrant tablets by mouth once a day Other Names: ORSERDU
Experimental: Cohort 4 Expansion Up to 30 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).	Drug: Samuraciclib Samuraciclib capsules by mouth once a day Drug: Elacestrant Dihydrochloride Elacestrant tablets by mouth once a day Other Names: ORSERDU

Outcome Measures

Primary Outcome Measures

Phase 1b (Dose-finding) [From the date of first dose of any study intervention (Day 1 Cycle 1) and through 28 days after the last dose of any study intervention]
Identification of Samuraciclib + Elacestrant combination, Phase 2, expansion dose level. Incidence and severity of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse events (NCI-CTCAE) v5.0. Safety will be assessed by monitoring treatment - emerged severe and dose limiting adverse events and clinically relevant changes in vital signs and clinical laboratory results
Phase 2 (Expansion) [From the date of first dose of any study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)]
Progression Free Survival (PFS) is defined as the time from the date of first dose of IMP (Cycle 1 Day 1) to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability) [From the date of first dose of any study intervention through 28 days after the last dose of any study intervention]
Type, incidence, severity (as graded by CTCAE v5.0), seriousness and relationship to study medications of AEs and any laboratory abnormalities. Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.
Clinical Benefit Response (CBR) [From the date of first dose of any study intervention (Cycle 1 Day 1) to ≥ 24 weeks or until disease progression or death to any cause (assessed up to week 24)]
CBR is defined as the overall complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks according to RECIST version 1.1 recorded from enrolment until disease progression, or death due to any cause.
Overall response rate (ORR) [the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)]
ORR is defined as the proportion of participants with a reduction in tumor burden with CR or PR according to RECIST version 1.1. ORR will be estimated for participants who received at least 1 dose of IMP, had measurable disease at baseline and had a postbaseline tumor assessment.
Duration of Response (DOR) [From the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)]
DOR is defined as the time from the date of first documentation of objective tumor response (CR or PR) to the earliest documented disease progression per RECIST version 1.1
Best percent change in tumor size. [From the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)]
Best percent change in tumor size is defined as the percentage change in the sum of the longest diameters of target lesions
Samuraciclib plasma exposure: Cmax [Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)]
Plasma concentration for Samuraciclib
Elacestrant exposure: Cmax [Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)]
Plasma concentrations for Elacestrant
Samuraciclib plasma exposure: Ctrough [Cycle 1 Day 2 and 15; Day 2 of Cycle 2; Day 1 of Cycles 3-6 and end of treatment within 28 days of last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days)]]
Elacestrant exposure: Ctrough [Cycle 1 Day 2 and Day 15; Cycle 2 Day 2 of Cycle 2 and Day 1 of Cycles 3-6 and at end of treatment within 28 days of the last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days)]
Genotyping for ESR1 and TP53 mutations [Screening]
Genotyping for ESR1 and TP53 mutations to evaluate correlations between ESR1 and TP53 mutations and efficacy/safety findings

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of ER-positive, HER2-negative locally advanced or metastatic breast cancer.
Documented objective disease progression while on or within 6 months after the end of the most recent therapy.
Received prior AI in combination with a CDK4/6i as the last therapy
Known TP53 and ESR1 mutation status.
Participants must have measurable disease or bone only disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Pre/peri-menopausal participants must have commenced treatment with a luteinizing hormone-releasing hormone (LHRH) agonist at least 4 weeks prior to first dose of study intervention.
Eastern Cooperative Oncology Group (ECOG) performance status ≤1 with no deterioration over the past 2 weeks.
Expected life expectancy of >12 weeks in the judgement of the treating investigator.

Exclusion Criteria:

Inflammatory breast cancer.
Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
More than 1 line of endocrine treatment for locally advanced or metastatic disease treatment.
Inadequate hepatic, renal, and bone marrow function.
Clinically significant cardiovascular disease.
Any current or prior central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
Pregnant or breastfeeding women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 43 - Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
2	Site 38 - Northwestern University, Feinberg School of Medicine, Northwestern University	Chicago	Illinois	United States	60611
3	Site 40 - Massachusetts General Hospital	Boston	Massachusetts	United States	02114-2696
4	Site 42 - Dana-Farber Cancer Institute, EDDC	Boston	Massachusetts	United States	02215
5	Site 35 - Cleveland Clinic, Taussig Cancer Institute	Cleveland	Ohio	United States	44106
6	Site 34 -The University of Texas, MD Anderson Cancer Center, Nellie B. Connally Breast Center	Houston	Texas	United States	77030
7	Site 41 - The START Center for Cancer Care, South Texas Oncology and Hematology	San Antonio	Texas	United States	78229
8	Site 32 - Swedish Medical Center, Swedish Cancer Institute (SCI),Cherry Hill Campus	Seattle	Washington	United States	98122
9	Site 81 - Bergonie unicancer, Nouvelle-Aquitaine, L'Institut Bergonie	Bordeaux		France
10	Site 80 - Centre Jean Bernard, Clinique Victor Hugo	Le Mans		France
11	Site 84 - UNICANCER, Centre Leon-Berard (CLB)	Lyon		France
12	Site 83 - Institut Paoli Calmettes (IPC)	Marseille		France
13	Site 85 - Institut Curie	Paris		France
14	Site 82 - Institut de Cancerologie de Ouest (ICO)	Saint-Herblain		France
15	Site 65 - Complexo Hospitalario Universitario A Coruña	A Coruña		Spain
16	Site 64 - Hospital Clinic de Barcelona (Hospital Clinic i Provincial)	Barcelona		Spain
17	Site 68 -Hospital Universitario Vall d'Hebron	Barcelona		Spain
18	Site 61 - Institut Catala d'Oncologia (ICO), Hospital Duran i Reynals Location	L'Hospitalet De Llobregat		Spain
19	Site 62 - Universidad de Navarra, Clinica Universidad de Navarra (CUN)	Madrid		Spain
20	Site 63 - South Texas Accelerated Research Therapeutics, CIOCC, Hospital Madrid Norte-Sanchinarro	Madrid		Spain
21	Site 66 - Hospital Clinico San Carlos	Madrid		Spain
22	Site 69 - Universidad de Navarra - Clinica Universidad de Navarra (CUN)	Pamplona		Spain
23	Site 60 - NEXT Oncology EU Hospital Universitario Quiron Salud Madrid	Pozuelo de Alarcon		Spain
24	Site 67 - Universidad de Sevilla, Hospital Universitario Virgen Macarena	Sevilla		Spain
25	Site 12 - Belfast City Hospital	Belfast		United Kingdom
26	Site 4 - The Christie NHS Foundation Trust	Manchester		United Kingdom
27	Site 13 - Nottingham City Hospital	Nottingham		United Kingdom
28	Site 2 - Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford		United Kingdom	OX3 7LE