Samuraciclib + Elacestrant for Advanced Breast Cancer

(SUMIT-ELA Trial)

Not currently recruiting at 26 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Carrick Therapeutics Limited

Must be taking: LHRH agonists

Disqualifiers: Inflammatory breast cancer, active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two drugs, samuraciclib and elacestrant, for treating advanced breast cancer that is hormone receptor-positive and HER2-negative. The researchers aim to determine how well these drugs work together to slow or stop cancer growth. This trial may suit individuals who have experienced disease progression after their most recent therapy and have a specific type of breast cancer. Participants must have previously taken certain cancer treatments and have a known status for particular genetic mutations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both samuraciclib and elacestrant have been tested in earlier studies. These studies suggest that the combination treatment is generally well-tolerated by participants. Some patients experienced side effects, but these were usually manageable.

For example, in previous trials, samuraciclib slowed disease progression in some breast cancer patients, indicating its effectiveness and safety. Elacestrant, the other part of the treatment, has also been used in other studies and is known for its manageable side effects.

Since this trial is in the early stages, researchers are still determining the safest and most effective doses for this combination. However, the prior testing of both drugs in humans provides some reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about samuraciclib combined with elacestrant for advanced breast cancer because these drugs offer a new way to tackle the disease. Unlike traditional treatments like chemotherapy, which often target rapidly dividing cells in general, this combination focuses specifically on cancer cell growth pathways. Samuraciclib is a CDK7 inhibitor, which means it blocks a protein that cancer cells need to grow, potentially leading to fewer side effects than standard chemotherapy. Meanwhile, elacestrant targets estrogen receptors, which are often involved in breast cancer progression, offering a more precise attack on the cancer. Together, these drugs might offer a more targeted and potentially effective treatment for patients with advanced breast cancer.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

Research has shown that combining samuraciclib and elacestrant may be promising for treating advanced breast cancer. In this trial, participants will receive different dosages of samuraciclib and elacestrant in various cohorts. Samuraciclib has helped patients live longer without their disease worsening, particularly those with hormone receptor-positive breast cancer who lack certain genetic mutations or cancer spread to the liver. Elacestrant blocks estrogen's effects on breast cancer cells. Together, these drugs might effectively slow cancer progression and improve patient outcomes. Early results suggest this combination could benefit those with advanced stages of the disease. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with HR+/HER2-negative advanced or metastatic breast cancer who've seen their disease progress after recent therapy. They must have had prior treatment with an AI and a CDK4/6 inhibitor, know their TP53 and ESR1 mutation status, and meet certain health criteria like good organ function and performance status.

Inclusion Criteria

Expected life expectancy of >12 weeks in the judgement of the treating investigator.

I know my TP53 and ESR1 mutation status.

I started treatment with an LHRH agonist at least 4 weeks ago.

Exclusion Criteria

I have had cancer spread to my brain or its coverings.

I haven't had any cancer except for certain skin cancers or cervical pre-cancer in the last 3 years.

My condition is inflammatory breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Initial dose escalation phase to confirm the safe dose of samuraciclib in combination with elacestrant

Up to 24 weeks

Regular visits for safety and PK data monitoring

Expansion

Expansion cohort to explore the efficacy of samuraciclib in combination with elacestrant

Up to 48 weeks

Regular visits for efficacy assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Elacestrant
• Samuraciclib

Trial Overview The study tests the safety and effectiveness of combining two drugs, Samuraciclib and Elacestrant Dihydrochloride, in treating advanced breast cancer. It's an international Phase 1b/2 trial where all participants will receive both medications to see how well they work together.

How Is the Trial Designed?

Group I: Cohort 4 Expansion Experimental Treatment 2 Interventions

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).

Group II: Cohort 3 Experimental Treatment 2 Interventions

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).

Group III: Cohort 2 Experimental Treatment 2 Interventions

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).

Group IV: Cohort 1 Experimental Treatment 2 Interventions

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).

Elacestrant is already approved in United States, European Union for the following indications:

Approved in United States as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Approved in European Union as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

Carrick Therapeutics Limited

Lead Sponsor

Trials

5

Recruited

290+

Berlin-Chemie AG Menarini Group

Industry Sponsor

Trials

4

Recruited

570+

Published Research Related to This Trial

Elacestrant, an oral selective estrogen receptor downregulator, was approved by the FDA in January 2023 for treating hormone receptor positive (HR+) HER2- advanced breast cancer, showing improved progression-free survival in patients with ESR1 mutations who had previously failed treatment with CDK 4/6 inhibitors and endocrine therapy.

Clinical trials indicate that elacestrant has a safety profile comparable to existing endocrine therapies and provides an effective alternative treatment option, especially for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. Hageman, E., Lussier, ME.[2023]

Elacestrant (RAD1901) effectively degrades estrogen receptors and inhibits the growth of estrogen receptor-positive (ER+) breast cancer cells in both laboratory and patient-derived models, showing significant antitumor activity.

The combination of elacestrant with other therapies like palbociclib or everolimus enhances its efficacy, suggesting it could be a valuable treatment option for patients with ER+ breast cancer, including those with resistant mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Bihani, T., Patel, HK., Arlt, H., et al.[2018]

The phase I trial assessed the safety and efficacy of elacestrant, a selective estrogen receptor degrader, specifically in patients with breast cancer.

This study represents an important step in evaluating new treatment options for breast cancer, focusing on a novel mechanism of action that targets estrogen receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Signs of Response to Elacestrant Seen in ER+ HER2- Breast Cancer. [2021]

Elacestrant, a selective estrogen receptor degrader, was found to be safe and well tolerated in a study involving 140 postmenopausal women, with doses up to 1000 mg daily not reaching the maximum tolerated dose.

The drug showed good oral bioavailability and a half-life of 27 to 47 hours, allowing for once-daily dosing, while effectively engaging estrogen receptors and demonstrating some ability to cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. Conlan, MG., de Vries, EFJ., Glaudemans, A., et al.[2021]

In a phase 3 study involving 666 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival to 24.8 months compared to 14.5 months with letrozole alone, indicating its efficacy as a treatment option.

While palbociclib plus letrozole showed better outcomes, it also resulted in higher rates of serious side effects, such as neutropenia (66.4% vs. 1.4% in the placebo group), highlighting the need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib and Letrozole in Advanced Breast Cancer. Finn, RS., Martin, M., Rugo, HS., et al.[2022]

Elacestrant (ORSERDU™) is a newly approved oral medication for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, following at least one line of endocrine therapy.

The drug specifically targets estrogen receptor-positive, HER2-negative breast cancer, and its approval in the USA marks a significant milestone in its development, with ongoing regulatory assessments in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: First Approval. Hoy, SM.[2023]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05963997

NCT05963997 | A Study of Samuraciclib and Elacestrant in ... This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult ...

2. carricktherapeutics.com carricktherapeutics.com/investors/news-events/press-releases/detail/21/carrick-therapeutics-announces-first-patient-dosed-in-phase

Press Releases Carrick Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of Samuraciclib in Combination with Elacestrant in Patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05963997?term=SAMURACICLIB&rank=3

A Study of Samuraciclib and Elacestrant in Participants ... This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult ...

4. targetedonc.com targetedonc.com/view/samuraciclib-shows-pfs-benefit-in-biomarker-selected-hr-breast-cancer

Samuraciclib Shows PFS Benefit in Biomarker-Selected ... Samuraciclib improved progression-free survival in HR+ advanced breast cancer patients without TP53 mutations or liver metastases.

5. withpower.com withpower.com/trial/phase-2-breast-neoplasms-6-2023-e019c

Samuraciclib + Elacestrant for Advanced Breast Cancer This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult ...