RGT-419B + Hormonal Therapy for Breast Cancer

Recruiting at 8 trial locations

Overseen By Regor Pharmaceuticals Central Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regor Pharmaceuticals Inc.

Must be taking: Hormonal therapy

Disqualifiers: Visceral metastases, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks (1 cycle)

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment, RGT-419B, for breast cancer that has advanced or spread to other parts of the body. Researchers aim to assess the safety and effectiveness of RGT-419B both alone and in combination with hormonal therapy, particularly for those whose cancer has worsened after previous treatments. Individuals with HR+, HER2- breast cancer, which has progressed despite prior treatment with CDK4/6 inhibitors and hormone therapy, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that major treatments like chemotherapy or radiation should not have been received within 14-28 days before starting the trial. It's best to discuss your current medications with the trial team.

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

Research has shown that RGT-419B has promising safety results from earlier studies. In one study involving patients with advanced breast cancer, RGT-419B proved to be safe and generally well-tolerated. The most common side effects included nausea and reduced appetite, but these were usually mild.

When combined with hormonal therapy, research suggests this combination can improve survival rates in breast cancer patients. Although specific safety data for the combination is limited, each treatment has been well-studied individually, providing some reassurance about their combined use.

Overall, the available data suggests that RGT-419B, whether used alone or with hormonal therapy, is likely safe for most patients, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RGT-419B because it offers a new approach to treating breast cancer by potentially enhancing the effectiveness of hormonal therapies. Unlike standard treatments like tamoxifen or aromatase inhibitors, which primarily target hormone receptors, RGT-419B may work through a novel mechanism that complements these therapies. This dual approach could improve outcomes for patients who don't fully respond to hormonal therapy alone, making it a promising addition to the current arsenal against breast cancer.

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

Research shows that RGT-419B may help treat advanced breast cancer. In this trial, participants will be assigned to one of two treatment arms. In Arm A, participants will receive RGT-419B alone. Earlier studies showed partial responses, meaning tumors got smaller. Initial findings suggest that this drug is safe and generally well-tolerated, even for those whose cancer has worsened despite previous treatments. In Arm B, participants will receive RGT-419B combined with hormonal therapy. This combination might improve survival rates, as similar combinations have done before, by targeting specific proteins that help cancer grow, potentially offering a new treatment option for patients. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with HR+, HER2- advanced or metastatic breast cancer who've had no more than one prior chemotherapy in this setting and less than three lines of CDK4/6i therapy. Participants must have an ECOG Performance Status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

My tumor is HR positive, HER2 negative, and can be measured.

I've had only one chemotherapy for advanced breast cancer, tolerated CDK4/6 inhibitors well, can take RT-419B, and recovered from past therapy side effects.

I have advanced breast cancer, tried <3 CDK4/6i therapies, and no more than 1 chemotherapy.

Exclusion Criteria

My cancer has spread to my organs, causing severe problems.

I haven't had major surgery or cancer treatment in the last 14 days.

I have not had radiation to more than a quarter of my bone marrow and my organs are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RGT-419B as monotherapy or in combination with Hormonal Therapy to evaluate safety, tolerability, and pharmacokinetics

4 weeks (1 cycle)

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety, tolerability, and efficacy through study completion

up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• RGT-419B

Trial Overview The study tests RGT-419B, a new oral medication, alone or combined with hormonal therapy. It's a phase I trial focusing on safety, how the body processes the drug (pharmacokinetics), and its initial effectiveness against certain types of breast cancer that progressed after previous treatments.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 1 Intervention

RGT-419B in combination with Hormonal Therapy

Group II: Arm A Experimental Treatment 1 Intervention

RGT-419B given alone as monotherapy

Who Is Running the Clinical Trial?

Regor Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

440+

Published Research Related to This Trial

Tamoxifen (TAM) was found to be the most effective treatment in a study involving hormone-dependent breast cancer models in mice, achieving a 100% efficacy rate, while medroxyprogesterone acetate (MPA) showed only 17% efficacy.

The combination of TAM and aminoglutethimide (AMG) enhanced the antitumor effect compared to either drug alone, likely due to AMG's ability to lower estrogen levels, which allows TAM to more effectively compete for estrogen receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental multihormone therapy on human breast carcinomas grown in nude mice]. Fukutomi, T.[2013]

Aminoglutethimide (AG) demonstrated a high efficacy as an aromatase inhibitor, achieving an average of 90.6% aromatase inhibition and 75.7% suppression of estradiol in 13 postmenopausal women with advanced breast cancer.

Rogletimide (RG) showed dose-dependent effects on aromatase inhibition and estradiol suppression, but even at the highest dose of 800 mg, it was less effective than AG, with a maximum aromatase inhibition of only 73.8% and estradiol suppression of 57.6%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. MacNeill, FA., Jones, AL., Jacobs, S., et al.[2019]

Aminoglutethimide may be an effective next step in hormone therapy for patients with metastatic breast cancer who have not responded to tamoxifen treatment.

This case highlights the sequential response to aminoglutethimide, suggesting its potential role in managing treatment-resistant breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to aminoglutethimide after tamoxifen therapy in advanced breast cancer. Allison, RW., Furnival, CM., Lee, JF., et al.[2021]

Targeted therapies, including CDK4/6 inhibitors and PI3K/AKT/mTOR pathway inhibitors, show promising clinical activity and acceptable toxicity in treating hormone receptor-positive, HER2-negative advanced breast cancer, offering new options beyond traditional endocrine therapy.

Immunotherapies targeting PD1/PD-L1 and CTLA-4 have demonstrated potential antitumor responses, indicating a new avenue for treatment in this breast cancer subtype, which is currently being explored in clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). Song, Y., He, L., Wang, Y., et al.[2021]

Hormone therapy is a key treatment for hormone receptor-positive breast cancer, but resistance can develop due to various genetic and epigenetic changes, leading to estrogen-independent tumor growth.

New therapeutic targets are being explored to overcome resistance, with two approved agents, everolimus and palbociclib, showing efficacy in treating metastatic HR+ breast cancer, though they require careful management of side effects like stomatitis and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Response to Hormone Therapy in Breast Cancer: New Targets, New Therapeutic Options. Rugo, HS., Vidula, N., Ma, C.[2022]

Targeted agents like CDK4/6 inhibitors have improved outcomes for patients with HR-positive, HER2-negative metastatic breast cancer compared to traditional endocrine therapies, but they come with complex and potentially severe adverse events that require careful management.

Despite the increased risk of hematologic toxicities and the need for more frequent physician visits, these side effects are generally manageable without needing to consult specialists, highlighting the importance of a multidisciplinary approach in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success. Cazzaniga, ME., Danesi, R., Girmenia, C., et al.[2020]

The NEOPAL trial demonstrated that the combination of letrozole and palbociclib in postmenopausal women with high-risk estrogen receptor-positive, HER2-negative breast cancer can achieve clinical and pathological responses similar to traditional chemotherapy, suggesting it may be a less toxic alternative.

At a median follow-up of 40.4 months, progression-free survival (PFS) and invasive-disease free survival (iDFS) rates were comparable between the letrozole-palbociclib group and the control group, indicating that this treatment strategy may effectively spare some patients from chemotherapy while maintaining good long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. Delaloge, S., Dureau, S., D'Hondt, V., et al.[2022]

Abiraterone, while primarily an androgen receptor blocker, has been shown to have paradoxical effects on estrogen receptor-positive breast cancer cells, stimulating growth in hormone-dependent cells and inducing cell death in estrogen-independent cells.

The study reveals that abiraterone increases estrogen receptor turnover and degradation, which could influence its effectiveness in treating different subtypes of estrogen receptor-positive breast cancer, particularly in cases with ESR1 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease. Simigdala, N., Pancholi, S., Ribas, R., et al.[2022]

Tamoxifen remains the first-line endocrine therapy for all stages of breast cancer, while newer agents like selective aromatase inhibitors are showing improved survival rates and are becoming preferred options for second-line therapy in metastatic cases.

Luteinizing hormone-releasing hormone agonists are effective for premenopausal women with advanced breast cancer, and ongoing trials are exploring the use of aromatase inhibitors as first-line treatments for metastatic disease and as adjuvant therapy for early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on endocrine therapy for breast cancer. Buzdar, AU., Hortobagyi, G.[2006]

In a study of 31 postmenopausal patients with advanced breast cancer, aminoglutethimide combined with hydrocortisone showed an overall response rate of 42%, indicating its effectiveness as a second-line hormonal treatment.

The response rates were 33% for patients who had never responded to tamoxifen and 47% for those who had previously responded, suggesting that aminoglutethimide may be particularly beneficial for patients with a history of tamoxifen response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced breast cancer with aminoglutethimide--response after previous tamoxifen treatment. Bezwoda, WR., Derman, DP., Browde, S., et al.[2014]

Hormone therapy for breast cancer has evolved over the last 20 years, with three major classes of medical treatments: antiestrogens, progestins, and aromatase inhibitors, each showing varying efficacy in patient response.

Antiestrogens can lead to remission in about one-third of patients, while progestins are effective in approximately 40%, and combination therapies, including second-line hormonotherapy, can achieve objective responses of 32 to 46% in patients who previously responded to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hormone therapy of breast cancer in the metastatic phase in menopausal women]. Namer, M.[2016]

Endocrine therapy, particularly the use of tamoxifen and aromatase inhibitors, has significantly improved survival rates in estrogen receptor positive breast cancer, with recent studies suggesting that extending tamoxifen treatment from 5 to 10 years may be beneficial.

The development of resistance to endocrine therapy is a major challenge, but combining treatments like the mTOR inhibitor everolimus with endocrine therapy has shown promise in redefining treatment strategies for metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer: current and future endocrine therapies. Palmieri, C., Patten, DK., Januszewski, A., et al.[2018]

Ribociclib combined with fulvestrant significantly improves progression-free survival (PFS) and overall survival (OS) in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, particularly in those with limited prior treatment.

The safety profile of ribociclib is manageable, with myelosuppression being a common side effect, while other toxicities like hepatobiliary issues and QTc prolongation occur at low rates, indicating it can be a viable treatment option in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib plus fulvestrant in the treatment of breast cancer. Neven, P., Sonke, GS., Jerusalem, G.[2021]

CDK4/6 inhibitors have significantly improved progression-free survival in patients with metastatic hormone receptor-positive breast cancer, highlighting their efficacy in overcoming endocrine resistance.

The optimal sequencing of therapies for these patients should consider individual factors such as medical history, previous treatments, quality of life, and side effects, ensuring personalized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming endocrine resistance in metastatic hormone receptor-positive breast cancer. D'Souza, A., Spicer, D., Lu, J.[2019]

Endocrine therapy is the recommended first-line treatment for hormone receptor-positive advanced breast cancer, utilizing methods like estrogen receptor blockers and aromatase inhibitors to manage the disease.

Despite the effectiveness of these therapies, about 25% of patients may experience primary or acquired resistance, highlighting the need for new strategies to overcome this challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy in post-menopausal women with metastatic breast cancer: From literature and guidelines to clinical practice. Sini, V., Cinieri, S., Conte, P., et al.[2018]

Citations

1. researchgate.net researchgate.net/publication/380308701_Abstract_PO3-18-06_First-in-human_phase_1A_study_of_RGT-419B_a_next_generation_CDK4_inhibitor_in_patients_pts_with_hormone_receptor_positive_HR_HER2-_advancedmetastatic_breast_cancer_ABC_who_progresse

Abstract PO3-18-06: First-in-human phase 1A study of RGT ... Tumor assessments (RECIST v1.1) of pts in the first 3 cohorts treated with RGT-419B monotherapy (25-150 mg QD) showed partial responses in 2 pts ...

2. clin.larvol.com clin.larvol.com/trial-detail/NCT05304962

FIH Study of RGT-419B Alone and With Endocrine Therapy ... Across 12 patients with HR+HER2- ABC who have progressed on CDK4/6is and ET, RGT-419B administered as oral (PO) monotherapy in continuous 28-day cycles was safe ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO3-18-06/744989/Abstract-PO3-18-06-First-in-human-phase-1A-study

First-in-human phase 1A study of RGT-419B, a next ... RGT-419B administered as once daily monotherapy also demonstrated preliminary evidence of efficacy as well. Dose expansions of RGT-419B as a ...

4. prnewswire.com prnewswire.com/news-releases/regor-announces-promising-safety-and-single-agent-efficacy-data-evaluating-rgt-419b-in-hrher2--advanced-breast-cancer-patients-who-have-progressed-on-cdk46-inhibitors-and-endocrine-therapy-302009555.html

Regor Announces Promising Safety And Single Agent ... The promising single agent efficacy of RGT-419B is consistent with the preclinical data from CDK4/6i resistant breast cancer models. "RGT-419B ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05304962

NCT05304962 | FIH Study of RGT-419B Alone and With ... This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of RGT- ...

6. oncologypipeline.com oncologypipeline.com/apexonco/regors-selective-approach-attracts-roche

Regor's selective approach attracts Roche | ApexOnco At ESMO the company claimed a 28% response rate among 18 ER-positive, HER2-negative breast cancer patients who had all received prior CDK4/6 ...