Endocrine Therapy + Palbociclib + Avelumab for Breast Cancer

(ImmunoADAPT Trial)

Not currently recruiting at 5 trial locations

Overseen By Sidney Kimmel Cancer Center Clinical Research Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Endocrine therapy

Must not be taking: SSRIs, Immunosuppressive therapy

Disqualifiers: Metastatic disease, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 34

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatment combinations for people with estrogen receptor-positive breast cancer. It compares standard hormone therapy with and without palbociclib, a drug that may help prevent cancer cell growth. After the initial treatment phase, all participants will receive avelumab, an immune system booster, before undergoing breast surgery. Ideal participants have stage II-III breast cancer that can be felt or seen on an ultrasound.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in breast cancer treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop using SSRIs and certain other medications at least 4 days before enrolling, unless there are no good alternatives and your doctor discusses it with the Study Chair. You also cannot be on immunosuppressive therapy within 2 weeks of starting the study.

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

Research has shown that hormone therapy is a well-known treatment for breast cancer that relies on estrogen to grow. It significantly lowers the chance of the cancer returning. Studies have found that extending hormone therapy from five to ten years can further reduce the risk of recurrence.

Research indicates that palbociclib is generally well-tolerated when combined with hormone therapy. Common side effects include tiredness and low blood cell counts, but these can usually be managed by adjusting the dose or with additional care.

Both treatments are already used for breast cancer, so their safety is well understood. However, it is important to monitor for side effects with any treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine endocrine therapy and palbociclib with avelumab to tackle ER-positive breast cancer in a novel way. Unlike standard treatments that typically focus on hormone therapy alone, palbociclib adds an extra punch by inhibiting cancer cell growth through a different pathway, specifically targeting the proteins that help cancer cells divide and multiply. Avelumab, an immunotherapy drug, is also included to potentially boost the immune system's ability to fight cancer cells. This combination approach is thought to be more effective by attacking the cancer from multiple angles, offering hope for better outcomes.

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

Research has shown that hormone therapy (HT) can significantly lower the risk of breast cancer recurrence and reduce mortality. Studies have found that tamoxifen, a common HT drug, can decrease the risk of cancer returning by 40% and reduce deaths by 30%. In this trial, some participants will receive endocrine therapy alone, while others will receive endocrine therapy with palbociclib. Adding palbociclib to HT has been shown to help patients with hormone receptor-positive breast cancer live longer. Real-world evidence suggests that this combination can extend life, with patients experiencing better overall survival rates. Together, these treatments offer a promising approach to managing breast cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Cesar A. Santa-Maria, MD, MSCI

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage II-III estrogen receptor positive breast cancer, who haven't had metastatic disease or inflammatory breast cancer. They must have good organ function and performance status, agree to use contraception, and not be on certain medications or treatments that could interfere.

Inclusion Criteria

Adequate organ and bone marrow function within 28 days prior to registration

You are able to perform daily activities with little or no difficulty.

Females of child-bearing potential and males must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days following completion of therapy

Exclusion Criteria

Use of SSRIs and/or any concomitant use of medications outlined in section 6.5 within 4 days prior to enrollment. If patients are on stable doses and there are no good alternatives, the treating physician may discuss with Study Chair

May not be receiving any other investigational agents

May not be receiving immunosuppressive therapy within 2 weeks of study entry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive endocrine therapy +/- palbociclib for 1 cycle, followed by 3 cycles of avelumab with endocrine therapy +/- palbociclib

16 weeks

Biopsy and MRI at Cycle 2, Day 1; Avelumab every 14 days

Surgery

Participants undergo breast surgery after completing treatment cycles

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Adverse events assessed 30 days post-therapy

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Endocrine therapy
• Palbociclib

Trial Overview The study tests if adding palbociclib to endocrine therapy before surgery improves outcomes in breast cancer patients. After initial treatment, avelumab is added for three cycles before surgery. Participants are randomly assigned to receive either just endocrine therapy or the combination with palbociclib.

How Is the Trial Designed?

Group I: Endocrine Therapy Active Control 2 Interventions

Eligible patients with ER-positive breast cancer will undergo a biopsy and be randomized to receive endocrine therapy (ET) versus endocrine therapy with palbociclib (PET) in a 1:2 ratio. A 1:2 ratio means that twice as many participants will be assigned to the PET arm as compared to the ET arm. After 1 cycle (28 days) another biopsy will be obtained, and both arms will receive avelumab (A) for 3 additional cycles. Patients will then undergo breast surgery.

Group II: Endocrine Therapy with Palbociclib Active Control 3 Interventions

Eligible patients with ER-positive breast cancer will undergo a biopsy and be randomized to receive endocrine therapy (ET) versus endocrine therapy with palbociclib (PET) in a 1:2 ratio. A 1:2 ratio means that twice as many participants will be assigned to the PET arm as compared to the ET arm. After 1 cycle (28 days) another biopsy will be obtained, and both arms will receive avelumab (A) for 3 additional cycles. Patients will then undergo breast surgery.

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

Approved in United States as Tamoxifen for:

• Adjuvant treatment of ER-positive early-stage breast cancer
• Treatment of metastatic breast cancer
• Risk reduction of breast cancer in high-risk women

Approved in United States as Anastrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Letrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Exemestane for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Fulvestrant for:

• Treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer
• Treatment of postmenopausal women with HR-positive advanced breast cancer with disease progression on endocrine therapy

Approved in United States as Elacestrant for:

• Treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Approved in European Union as Tamoxifen for:

• Adjuvant treatment of ER-positive early-stage breast cancer
• Treatment of metastatic breast cancer
• Risk reduction of breast cancer in high-risk women

Approved in European Union as Anastrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Letrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Exemestane for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Fulvestrant for:

• Treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer
• Treatment of postmenopausal women with HR-positive advanced breast cancer with disease progression on endocrine therapy

Approved in European Union as Elacestrant for:

• Treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Allegheny Health Network

Collaborator

Trials

6

Recruited

1,100+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

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

Allegheny Health Network

Collaborator

Trials

7

Recruited

1,700+

Published Research Related to This Trial

Tamoxifen, while a long-standing treatment for early breast cancer, only prevents about half of relapses and can lead to serious side effects like endometrial hyperplasia and venous thromboembolism due to its estrogenic activity.

Aromatase inhibitors are emerging as a more effective alternative, showing benefits in various treatment settings, including extending therapy after tamoxifen and providing upfront adjuvant therapy, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. Chahine, G., Howayek, M., Atallah, D.[2013]

Adjuvant endocrine treatment is crucial for postmenopausal women with hormone receptor-positive breast cancer, with options including tamoxifen and aromatase inhibitors, each having unique side effects.

For premenopausal women, tamoxifen is the standard treatment, and ongoing research is exploring the potential benefits of adding ovarian suppression to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for early-stage breast cancer. Burstein, HJ., Griggs, JJ.[2010]

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]

Palbociclib, a selective CDK4/6 inhibitor, has been shown to be effective when combined with letrozole or fulvestrant in treating HR+/HER2- advanced breast cancer, particularly in cases where patients have developed resistance to standard endocrine therapies.

The combination of palbociclib with endocrine therapy is well tolerated by patients, making it a valuable addition to treatment options for locally advanced and metastatic ER+/HER2- breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Palbociclib combinations as new therapeutic strategies in the treatment of HR+/HER2- advanced breast cancer]. Boér, K.[2019]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

Endocrine therapy is the first-line treatment for women with hormone receptor-positive metastatic breast cancer due to its effectiveness and lower toxicity compared to chemotherapy, aiming to maintain quality of life and prolong survival.

Various classes of endocrine therapies, including aromatase inhibitors and selective estrogen modulators, are available, but resistance to these treatments eventually develops, highlighting the need for optimal timing and sequencing of therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extending the clinical benefit of endocrine therapy for women with hormone receptor-positive metastatic breast cancer: differentiating mechanisms of action. Glück, S.[2014]

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10453164/

Extended Adjuvant Endocrine Therapy in Early Breast ... Taking tamoxifen for 5 years has been shown to reduce the risk of breast cancer recurrence by 40% and mortality by 30% compared to patients ...

2. esmoopen.com esmoopen.com/article/S2059-7029(25)00926-3/fulltext

Extended adjuvant endocrine therapy in early breast cancer 10 years of adjuvant ET is superior to 5 years in reducing recurrences. Seven to eight years of ET improves outcomes compared with 5 years.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e12516

The impact of adjuvant endocrine therapy on outcomes in ... This study demonstrates that endocrine therapy significantly improves survival outcomes in patients with ER-low positive, HER2-negative breast cancer.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1701830

20-Year Risks of Breast-Cancer Recurrence after Stopping ... After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years.

5. nature.com nature.com/articles/s41523-023-00523-4

An emerging generation of endocrine therapies in breast ... Anti-estrogen therapy is a key component of the treatment of both early and advanced-stage hormone receptor (HR)-positive breast cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5951224/

Effect of first-line endocrine therapy in patients with ... Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human ...

7. breastsurgeons.org breastsurgeons.org/docs/statements/asbrs-endocrine-therapy.pdf

Endocrine Therapy for the Management and Risk ... Endocrine therapy reduces the risk of developing estrogen receptor positive (ER+) breast cancer by 50% or more in the above groups of patients; ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6095972/

Current Landscape of Targeted Therapies for Hormone ... In this review, we will discuss management and ongoing challenges in the treatment of advanced HR positive, HER2 negative breast cancer.