255 Participants Needed

LEE011 + BYL719 + Letrozole for Breast Cancer

Recruiting at 38 trial locations
Age: 18+
Sex: Female
Trial Phase: Phase 1 & 2
Sponsor: Novartis Pharmaceuticals
Must be taking: Letrozole
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on hormone replacement therapy that cannot be discontinued. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Letrozole for breast cancer?

Research shows that Letrozole significantly improves disease-free survival in postmenopausal women with hormone-responsive early breast cancer compared to tamoxifen, and it is effective as both adjuvant and extended adjuvant therapy.12345

Is the combination of LEE011, BYL719, and Letrozole safe for humans?

Letrozole, one of the drugs in the combination, is generally safe for humans with mostly mild side effects like hot flashes, joint pain, and nausea. It has been widely used in breast cancer treatment and is approved in many countries.12678

What makes the drug combination of LEE011, BYL719, and Letrozole unique for breast cancer treatment?

The combination of LEE011 (a CDK4/6 inhibitor), BYL719 (a PI3K inhibitor), and Letrozole (an aromatase inhibitor) is unique because it targets multiple pathways involved in breast cancer cell growth, potentially offering a more comprehensive approach to treatment compared to using Letrozole alone.2591011

What is the purpose of this trial?

The purpose of this trial is to inform the future clinical development of the two investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha inhibitor).This is a multi-center, open-label Phase Ib study. The Phase Ib dose escalation will estimate the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole (Arms 3 and 4).The Phase Ib dose escalation part will be followed by Phase Ib dose expansions to further characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the combinations. Optional crossover for patients who have progressed while on dose escalation or dose expansion with doublet treatment on Arms 1 or 2 to be treated with the triplet combination (Arm 3) after the determination of the RP2D for Arm 3; is no longer permitted after protocol amendment 6.Approximately 270 adult women with ER+/HER2- locally advanced or metastatic breast cancer will be enrolled.

Research Team

NP

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for postmenopausal women with advanced ER+/HER2- breast cancer who haven't had systemic treatment in the advanced setting, except possibly letrozole for up to one month. They can have had (neo)adjuvant therapy if they've been disease-free for over a year since completion. Exclusions include recent major surgery, other cancers within 3 years, heart issues, active brain metastases, and certain diabetes conditions.

Inclusion Criteria

I had early-stage breast cancer treatment and have been disease-free for over a year.
I may have had multiple hormone treatments but only one chemotherapy for advanced cancer.
I haven't had systemic treatment for advanced cancer, except possibly letrozole for up to a month.
See 2 more

Exclusion Criteria

My heart does not function properly.
I have diabetes or had gestational diabetes.
I have pancreatitis.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase Ib dose escalation to estimate the MTD and/or RP2D for the combinations

28 days per cycle
Multiple visits for dose adjustments and monitoring

Dose Expansion

Phase Ib dose expansions to further characterize safety, tolerability, PK, and preliminary clinical anti-tumor activity

18-24 months
Regular visits for safety and PK assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • BYL719
  • LEE011
  • Letrozole
Trial Overview The study tests two drugs: LEE011 (a CDK4/6 inhibitor) and BYL719 (a PI3K-alpha inhibitor), both combined with letrozole. It's an open-label Phase Ib trial aiming to find the maximum tolerated doses of these combinations and their preliminary effectiveness against breast cancer.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: LEE011+ BYL719+letrozole Arm 4Experimental Treatment3 Interventions
LEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day
Group II: LEE011 + letrozole Arm 1Experimental Treatment2 Interventions
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day
Group III: LEE011 + BYL719 + letrozole Arm 3Experimental Treatment3 Interventions
LEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day
Group IV: BYL719 + letrozole Arm 2Experimental Treatment2 Interventions
BYL719 - daily (dose escalating) letrozole - 2.5 mg/day

Find a Clinic Near You

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials
2,963
Recruited
4,275,000+
Founded
1996
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Gleevec, Cosentyx, Entresto, Kisqali
Dr. Vas Narasimhan profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a study of 150 breast cancer patients, those receiving sequential treatment with letrozole and tamoxifen showed a higher overall response rate and fewer adverse reactions compared to those on letrozole alone.
Both treatment methods resulted in similar survival rates, but the sequential therapy group had a significantly lower recurrence rate and better improvement in blood lipid levels, indicating a potentially better prognosis.
Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma.Lu, X., Qian, C.[2023]
Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.
In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.
Letrozole: a review of its use in postmenopausal women with breast cancer.Simpson, D., Curran, MP., Perry, CM.[2018]
Letrozole is more effective than tamoxifen for adjuvant therapy in postmenopausal women with hormone-responsive early breast cancer, and it is well tolerated by patients.
Extended therapy with letrozole after tamoxifen treatment is more effective than placebo, making it a valuable treatment option while ongoing trials investigate the best duration and comparison with other aromatase inhibitors.
Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.Keating, GM.[2021]

References

Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. [2018]
Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. [2023]
Results of letrozole in postmenopausal women after tamoxifen treatment for advanced breast cancer. [2019]
Letrozole: a review of its use in postmenopausal women with breast cancer. [2018]
Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. [2021]
[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. [2018]
The FACE trial: letrozole or anastrozole as initial adjuvant therapy? [2018]
The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98. [2022]
The aromatase inhibitor letrozole and inhibitors of insulin-like growth factor I receptor synergistically induce apoptosis in in vitro models of estrogen-dependent breast cancer. [2022]
Letrozole as primary medical therapy for locally advanced and large operable breast cancer. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. [2018]
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