A study to test the effect of Samuraciclib in Combination with Elacestrant in Participants with Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2-negative (HER2-) breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Carrick Therapeutics Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Oct 2023 → 6 Mar 2026

Decision date (initial)

2023-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

• Phase 1b (Dose Finding): Determine the recommended Phase 2 dose (RP2D) of samuraciclib and elacestrant in combination.
• Phase 2 (Expansion): To assess the efficacy of samuraciclib and elacestrant in combination in terms of progression-free survival (PFS) as per local investigator assessment.

Secondary objectives 4

1. To characterize the safety and tolerability of samuraciclib and elacestrant in combination.
2. To evaluate the pharmacokinetics (PK) of samuraciclib and elacestrant when used in combination and, if identified, explore any potential drug-drug interactions.
3. To further assess the biological and antitumor activity of samuraciclib and elacestrant in combination.
4. To evaluate correlations between estrogen receptor 1 (ESR1) and tumor suppressor p53 (TP53) mutations and efficacy/safety findings in this participant population.

Conditions and MedDRA coding

Breast Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically confirmed diagnosis of carcinoma of the breast with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.
2. Documentation of ER-positive with or without progesterone receptor (PgR)-positive tumor based on most recent tumor biopsy utilizing an assay consistent with local standards. • ER-positivity is defined as ≥10% positive stained cells regardless of the PgR-result (Hammond et al., 2010; Allison et al., 2020).
3. Documentation of HER2 negativity based on local testing on most recent tumor biopsy. • HER2-negativity is defined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescent in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver-enhanced in situ hybridization [SISH] defined as a HER2/chromosome 17 FISH (CEP17) ratio <2 or for single probe assessment a HER2 copy number <4 • Biopsy of first recurrence is recommended, in case no tumor biopsy was performed after initial resection of the primary tumor, the original tumor tissue serves as basis for assessment of ER/PgR and HER2 status • Assessment of ER, PgR, and HER2 status will be based on results from local pathology laboratories.
4. Must have 1 of the following as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: • Measurable disease • Bone only disease with evaluable lesions. Participants who have had prior radiation to bone must have at least 1 evaluable lesion in a nonirradiated area. For clarity bone lesions must be evaluable, but do not need to be measurable.
5. Participants must have documented objective disease progression while on or within 6 months after the end of the most recent therapy.
6. Participants must have received an aromatase inhibitor in combination with a CDK4/6 inhibitor in one of the following settings: • Participants must have received at least 6 months of clinical benefit on this line of therapy to be eligible. Participants who received <6 months CDK4/6 inhibitor due to tolerability issues may still enter the study provided at least 6 months aromatase inhibitor was received. • Adjuvant setting, if the disease-free interval between initiation of endocrine therapy and first line treatment of locally advanced or metastatic disease was >24 months.
7. Expected life expectancy of greater than 12 weeks.

Exclusion criteria 9

1. Prior therapy with a Selective estrogen receptor degrader (SERD) or other investigational SERDs or alike agents in the advanced/metastatic setting.
2. Prior treatment with cytotoxic chemotherapy for locally advanced or metastatic BC.
3. Prior treatment with a mammalian target of rapamycin (mTOR) inhibitor including, but not limited to, everolimus.
4. Inadequate hepatic, renal, bone marrow, or cardiac function, specified as follows: • Hepatic • Renal • Bone marrow • Cardiovascular
5. Known central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
6. More than 1 line of endocrine treatment for locally advanced or metastatic disease treatment
7. Inflammatory BC
8. Prior treatment with a phosphatidylinositol-3-kinase (PI3K) inhibitor, including, but not limited to alpelisib.
9. Prior treatment with an AKT (protein kinase B, or Akt) inhibitor, including, but not limited to capivasertib.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Phase 1b (Dose-finding): ): Identification of combination, Phase 2, expansion dose level. Dose- limiting toxicities and type, incidence, severity (as graded by CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities
2. • Phase 2 (Expansion): PFS, defined as the time from enrollment until disease progression or death

Secondary endpoints 8

1. • Type, incidence, severity (as graded by CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities
2. • Clinical benefit response (CBR) 24 weeks (a complete or partial response, or stable disease (SD) for at least 24 weeks).
3. • Overall Response Rate (ORR), defined as the proportion of participants with a reduction in tumor burden (PR and/or CR in accordance with RECIST v1.1) of a predefined amount
4. • Duration of Response (DOR), defined as the time from documentation of tumor response (PR and/or CR) to disease progression.
5. • Best percent change in tumor size.
6. • Plasma concentrations and PK parameters of samuraciclib
7. • Plasma concentrations and PK parameters of elacestrant
8. • Correlations between ESR1 and TP53 mutations and efficacy/safety findings in this participant population

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Carrick Therapeutics Limited

Sponsor organisation

Carrick Therapeutics Limited

Address

Block 1, Blanchardstown Corporate Park 1 Blanchardstown Corporate Park 1

City

Dublin 15

Postcode

D15 AKK1

Country

Ireland

Scientific contact point

Organisation

Carrick Therapeutics Limited

Contact name

Sheila O'Mahony

Public contact point

Organisation

Carrick Therapeutics Limited

Contact name

Sheila O'Mahony

Third parties 8

Locations

2 EU/EEA countries · 16 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 16 files

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

Application history

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