Endocrine Therapy + Palbociclib + Avelumab for Breast Cancer

(ImmunoADAPT Trial)

Recruiting at 4 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

33 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug combination of endocrine therapy, palbociclib, and avelumab for breast cancer?

Research shows that combining palbociclib with endocrine therapy is effective for treating hormone receptor-positive advanced breast cancer, as it can overcome resistance to endocrine therapy and prolong the time before the cancer progresses. This combination is well-tolerated and helps maintain quality of life for patients. ^{1 2 3 4 5}

Is the combination of endocrine therapy and palbociclib generally safe for breast cancer patients?

The combination of endocrine therapy and palbociclib is generally well tolerated in breast cancer patients, with neutropenia (a low level of neutrophils, a type of white blood cell) being the most common side effect. Serious adverse events are infrequent, and the combination is considered an important addition to breast cancer treatment options. ^{4 6 7 8 9}

What makes the drug combination of Endocrine Therapy, Palbociclib, and Avelumab unique for breast cancer treatment?

This drug combination is unique because it combines endocrine therapy with palbociclib, a CDK4/6 inhibitor that helps overcome resistance to hormone therapy, and avelumab, an immunotherapy drug, potentially enhancing the overall treatment efficacy for HR+/HER2- advanced breast cancer. ^{1 4 9 10 11}

What is the purpose of this trial?

Eligible patients with estrogen receptor 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. 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.

Research Team

Cesar A. Santa-Maria, MD, MSCI

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women. [2018]

2. England pubmed.ncbi.nlm.nih.gov

The safety of palbociclib for the treatment of advanced breast cancer. [2018]

3. United States 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. [2014]

4. Hungary pubmed.ncbi.nlm.nih.gov

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

5. Ireland pubmed.ncbi.nlm.nih.gov

Breast cancer: current and future endocrine therapies. [2018]

6. Lebanon pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. [2013]

7. Japan pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine monotherapy for postmenopausal early breast cancer patients with hormone-receptor positive: a systemic review and network meta-analysis. [2023]

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

Adjuvant hormonal therapy for early-stage breast cancer. [2010]

9. France pubmed.ncbi.nlm.nih.gov

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

10. Austria pubmed.ncbi.nlm.nih.gov

CDK4/6 inhibition in luminal breast cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]