Samuraciclib + Elacestrant for Advanced Breast Cancer

(SUMIT-ELA Trial)

Recruiting at 23 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

49 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination Samuraciclib and Elacestrant for advanced breast cancer?

Research shows that Elacestrant, a drug that targets estrogen receptors in breast cancer, has been effective in reducing tumor growth in various models of estrogen receptor-positive breast cancer. Additionally, similar drugs like palbociclib have shown improved outcomes when combined with other treatments, suggesting potential benefits of combination therapies. ^{1 2 3 4 5}

Is the combination of Samuraciclib and Elacestrant safe for humans?

Elacestrant, also known as Orserdu, is approved for treating certain types of advanced breast cancer and has been studied for its safety in humans. However, specific safety data for the combination of Samuraciclib and Elacestrant is not provided in the available research. ^{1 3 6 7 8}

What makes the drug combination of Samuraciclib and Elacestrant unique for advanced breast cancer?

The combination of Samuraciclib and Elacestrant is unique because Elacestrant is an oral selective estrogen receptor degrader (SERD) that targets estrogen receptors in breast cancer cells, including those with ESR1 mutations, which are often resistant to standard endocrine therapies. This combination aims to enhance treatment efficacy by exploiting the cancer's dependence on estrogen signaling, offering a novel approach for patients with advanced ER-positive, HER2-negative breast cancer. ^{1 3 6 7 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. [2021]

2. England 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. [2023]

3. United States 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Palbociclib and Letrozole in Advanced Breast Cancer. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Elacestrant: First Approval. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Modeling the novel SERD elacestrant in cultured fulvestrant-refractory HR-positive breast circulating tumor cells. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating Elacestrant in the Management of ER-Positive, HER2-Negative Advanced Breast Cancer: Evidence to Date. [2023]