Combo Therapy for Breast Cancer

Recruiting at 17 trial locations

Overseen By OP-1250-003 Study

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Olema Pharmaceuticals, Inc.

Must not be taking: PI3K inhibitors, mTOR inhibitors

Disqualifiers: Heart disease, Liver disease, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 56

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best combination of treatments for advanced breast cancer. Researchers are testing four pairings of the drug palazestrant (also known as OP-1250) with other medications to evaluate their effectiveness together. The trial seeks participants with advanced or metastatic breast cancer that is estrogen receptor-positive (ER+) and HER2-negative (HER2-). Participants should have undergone no more than two hormonal treatments for their cancer previously. 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 information does not specify if you need to stop taking your current medications. However, it does mention that you should not have received prior treatment with certain drugs like OP-1250, PI3K inhibitors, or mTOR inhibitors, depending on the treatment group.

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

Research shows that palazestrant (OP-1250) is generally safe when combined with other treatments. For instance, when paired with ribociclib (KISQALI®), it was well tolerated, with no unexpected side effects reported. Studies also indicate that palazestrant alone is safe for many patients with advanced breast cancer.

When used with alpelisib (PIQRAY®), palazestrant remained well-tolerated, indicating general safety. Similarly, combining palazestrant with everolimus did not introduce new safety issues, suggesting safety in this combination as well.

For the combination of palazestrant with atirmociclib, research is still in the early stages. Scientists are closely monitoring patient responses, and so far, no major problems have emerged.

In summary, while each combination remains under study, palazestrant with these treatments has shown promising safety results, indicating it is generally safe for use in these clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore novel combinations of Palazestrant with other drugs, aiming to enhance effectiveness against breast cancer. Unlike traditional options that often rely on single-agent therapies, these combinations target multiple pathways. For instance, Palazestrant combined with Ribociclib or Alpelisib can potentially improve outcomes by simultaneously inhibiting cancer cell growth and proliferation. Additionally, the use of Everolimus and Atirmociclib with Palazestrant introduces a fresh approach by targeting distinct molecular mechanisms, which might offer new hope for patients who have not responded well to existing treatments.

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

In this trial, participants will receive different combinations of palazestrant (OP-1250) with other drugs. Research has shown that combining palazestrant with ribociclib is promising for treating breast cancer. Specifically, this combination helped patients live without cancer progression for an average of 15.5 months, with 79% experiencing a positive effect. Another treatment arm will test palazestrant paired with alpelisib, which studies indicate helps patients with certain genetic mutations live longer without cancer progression. The effects of combining palazestrant with everolimus and atirmociclib are still under investigation, but early results suggest these combinations might help manage advanced breast cancer. Overall, these combinations are being researched for their potential to effectively fight cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Daniela Vecchio, PhD

Principal Investigator

Olema Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic HR+/HER2- breast cancer, who've had no more than one prior chemo and up to two hormone therapies. They should have a life expectancy of at least 6 months and be able to follow the study plan. Exclusions include other cancers, heart disease, liver disease not in early stages, recent serious blood clots or stroke, lung conditions like pneumonitis, or HIV.

Inclusion Criteria

Willing and able to participate and comply with all study requirements

Evaluable disease (measurable and non-measurable)

I am fully active or can carry out light work.

Exclusion Criteria

I have had pneumonitis or lung disease affecting the tissue and space around the air sacs.

I am HIV positive.

I haven't had a stroke or brain blood vessel issue in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluate the safety and pharmacokinetics of OP-1250 in combination with ribociclib, alpelisib, or everolimus to determine the RP2D

28 days

Visits every 28 days

Dose Expansion

Further evaluate the safety and pharmacokinetics of OP-1250 at the RP2D and provide an exploratory estimate of anti-tumor activity

Up to 1 year

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 35 days

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• OP-1250
• Ribociclib

Trial Overview The study tests OP-1250 combined with either ribociclib (Treatment Group 1) or alpelisib (Treatment Group 2). It's an open-label Phase 1b trial meaning both researchers and participants know which treatment is given. The goal is to assess safety and effectiveness of these combinations in treating breast cancer.

How Is the Trial Designed?

Group I: Palazestrant with Ribociclib Experimental Treatment 2 Interventions

Treatment Group 1: Palazestrant in combination with ribociclib (KISQALI®, Novartis Pharmaceuticals Corporation).

Group II: Palazestrant with Everolimus Experimental Treatment 2 Interventions

Treatment Group 3: Palazestrant in combination with everolimus

Group III: Palazestrant with Atirmociclib Experimental Treatment 2 Interventions

Treatment Group 4: Palazestrant in combination with atirmociclib

Group IV: Palazestrant with Alpelisib Experimental Treatment 2 Interventions

Treatment Group 2: Palazestrant in combination with alpelisib (PIQRAY®, Novartis Pharmaceuticals Corporation)

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

Approved in United States as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Approved in European Union as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant

Who Is Running the Clinical Trial?

Olema Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

970+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Published Research Related to This Trial

Alpelisib (PIQRAY®) is the first PI3K inhibitor approved for treating hormone receptor-positive metastatic breast cancer with PIK3CA mutations, showing promising clinical results that support its use in overcoming endocrine resistance.

The review highlights the pharmacodynamic and pharmacokinetic properties of alpelisib, along with safety and efficacy data from the Phase III SOLAR-1 trial, which led to its FDA approval, indicating its potential as a tailored treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. Mavratzas, A., Marmé, F.[2021]

In the MONALEESA-3 trial, the addition of ribociclib to fulvestrant significantly improved median progression-free survival (PFS) from 12.8 months to 20.5 months in patients with hormone receptor-positive, HER2-negative advanced breast cancer, indicating its efficacy as a treatment option.

The SANDPIPER trial showed that taselisib combined with fulvestrant extended PFS in patients with PIK3CA mutations, but it also resulted in a higher rate of severe adverse events (32% vs 9%), highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASCO 2018 highlights: metastatic breast cancer. Rinnerthaler, G., Gampenrieder, SP., Greil, R.[2020]

Ribociclib, a CDK 4/6 inhibitor, significantly improves median progression-free survival (PFS) in women with HR+/HER2- metastatic breast cancer when used in combination with endocrine therapy, with PFS ranging from 8 to 13 months across three phase III trials.

The treatment is well tolerated, particularly in elderly patients, and while it has some dose-limiting toxicities like neutropenia and QTc prolongation, it maintains health-related quality of life and reduces pain scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. Rascon, K., Flajc, G., De Angelis, C., et al.[2020]

The study established the recommended phase 2 doses (RP2D) for alpelisib (350 mg) and buparlisib (100 mg) when combined with tamoxifen and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, showing that both combinations were well-tolerated.

Patients treated with alpelisib experienced a longer progression-free survival of 25.2 months compared to 20.6 months for those on buparlisib, suggesting that alpelisib may be a more effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. Lu, YS., Lee, KS., Chao, TY., et al.[2021]

In the phase III MONALEESA-2 study involving 668 postmenopausal women with advanced HR+ HER2- breast cancer, treatment with ribociclib plus letrozole maintained health-related quality of life (HRQoL) scores similar to those receiving placebo plus letrozole.

Patients receiving ribociclib experienced a clinically meaningful reduction in pain as early as Week 8, which was sustained up to Cycle 15, indicating that ribociclib not only improves clinical outcomes but also enhances patient-reported outcomes related to pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2. Verma, S., O'Shaughnessy, J., Burris, HA., et al.[2022]

In a study of 554 Italian patients with hormone receptor-positive, HER2-negative advanced breast cancer, ribociclib combined with letrozole showed a clinical benefit rate of 71.7% and a median time to progression of 26.7 months, indicating effective treatment outcomes.

The treatment was associated with manageable safety profiles, with 98.9% of patients experiencing all-grade adverse events, primarily neutropenia, but health-related quality of life scores remained stable during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study. De Laurentiis, M., Caputo, R., Mazza, M., et al.[2022]

In a phase Ib study involving 26 patients with metastatic ER+ breast cancer, the combination of alpelisib and letrozole was found to be safe, with a maximum-tolerated dose of 300 mg/d and manageable side effects like hyperglycemia and fatigue.

The treatment showed a clinical benefit rate of 35%, particularly benefiting patients with PIK3CA mutations, where 44% experienced a lack of disease progression for at least 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer. Mayer, IA., Abramson, VG., Formisano, L., et al.[2022]

In a study of 76 women with hormone receptor-positive, HER2-negative metastatic breast cancer, alpelisib combined with endocrine therapy demonstrated a median progression-free survival of 5.2 months, indicating its effectiveness in a real-world setting.

However, about 31.6% of patients had to permanently discontinue alpelisib due to adverse events, with hyperglycemia being the most common serious side effect, highlighting the need for careful monitoring of patients on this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience. Sarfraz, H., Bari, S., Whiting, J., et al.[2023]

Alpelisib (Piqray™) is an oral PI3K inhibitor specifically targeting PI3Kα, showing efficacy in treating hormone receptor-positive, HER2-negative breast cancer in patients with a PIK3CA mutation.

The drug has been approved in the USA for use in combination with fulvestrant, marking a significant milestone in its development for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. Markham, A.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05508906

NCT05508906 | Phase 1b Study of OP-1250 (Palazestrant) ... This is a Phase 1b open-label, 2-part study in 3 treatment groups. The 3 treatment groups are as follows: Treatment Group 1: Palazestrant (OP-1250) in ...

2. ir.olema.com ir.olema.com/news-releases/news-release-details/olema-oncology-presents-updated-clinical-results-palazestrant

Release Details Palazestrant combined with ribociclib showed promising clinical activity including tumor responses, prolonged disease stabilization, and progression-free ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12210654/

advanced or metastatic breast cancer: phase 1/2 study results The RP2D of 120 mg/day palazestrant demonstrated evidence of antitumor activity, with a CBR of 45.7% and a median PFS of 4.8 months in the ...

4. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO4-04-12/744659/Abstract-PO4-04-12-A-Phase-1b-2-study-of

A Phase 1b/2 study of palazestrant (OP-1250) in combination ... Addition of the PIK3 inhibitor alpelisib to ET significantly improved progression-free survival in pts with PIK3CA-mutated, ER-positive, HER2- ...

5. ir.olema.com ir.olema.com/news-releases/news-release-details/olema-oncology-announces-new-data-phase-1b2-trial-palazestrant

Olema Oncology Announces New Data from the Phase 1b/ ... Palazestrant in combination with ribociclib demonstrated encouraging activity across all dose cohorts and subgroups; Median PFS was 15.5 ...

6. ir.olema.com ir.olema.com/static-files/dfb83ebb-df49-47a3-a585-ec416cc48954

A Phase 1b/2 Study of Palazestrant (OP-1250) in ... In a phase 1/2 study, palazestrant as monotherapy showed favorable safety, good ... advanced or metastatic breast cancer. *CBR is the proportion ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS1135

OPERA-01: A randomized, open-label, phase 3 study of ... A multicenter, randomized, open-label, phase 3 clinical trial comparing the efficacy and safety of palazestrant as a single agent to SOC ET.