Pembrolizumab With Carboplatin Compared to Carboplatin Alone in Breast Cancer Patients With Chest Wall Disease

NCT03095352 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CC#157521+167513TBCRC 044NCI-2018-00010
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 7

Brief Summary

This is a phase II multicenter study including breast cancer patients with chest wall disease that is hormone resistant (estrogen receptor (ER) positive/progesterone receptor (PR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer with progressive disease on 2 prior lines of hormonal therapy) or triple negative (ER negative/PR negative/HER2 negative, TNBC). A companion translational study is operating concurrently with the study described above. In this study, biomarker research to be performed on tumor biopsies and peripheral blood samples will be performed to explore the immunologic and genomic mechanism of action underlying treatment with pembrolizumab and carboplatin versus carboplatin alone. This protocol includes tissue and blood correlative exploratory endpoints including changes in tumor PD-L1 (programmed death ligand 1) gene expression, tumor and peripheral blood immune composition and cytokine expression, plasma tumor DNA, circulating tumor cells, and tumor myelocytomatosis (MYC) oncogene expression using tumor biopsy and peripheral blood testing before and after treatment; correlations with these markers and disease control rate will be assessed.

Conditions

Breast Cancer; Chest Wall Disease

Outcome Measures

Primary Outcomes (2)

• Disease Control Rate (DCR) at 18 Weeks

  The percentage of participants with Complete response (CR), Partial Response (PR), and stable disease (SD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 18 weeks of treatment in breast cancer patients with chest wall disease treated with pembrolizumab and carboplatin (Arm A) or carboplatin alone (Arm B) will be reported.

  Up to 18 weeks

• Median Progression Free Survival (PFS) at 18 Weeks

  PFS is defined as the time in months from observed objective response to disease progression at week 18 and will be summarized using estimates by the Kaplan-Meier method in order to account for any censoring participants by enrolling treatment arms (Arm A and Arm B only)

  Up to 18 weeks

Secondary Outcomes (3)

• DCR by Immune-related (ir) RECIST at 18 Weeks

  Up to 18 weeks

• Objective Response Rate (ORR)

  Up to 18 weeks

• Number of Participants With Treatment-related Adverse Events (AEs)

  Up to 18 months

Study Arms (2)

Arm A: Pembrolizumab + Carboplatin

EXPERIMENTAL

Participants receive carboplatin intravenously (IV) and pembrolizumab IV over 30 minutes on day 1. Participants who are HER2+ also receive trastuzumab IV every 3 weeks. Treatment repeats every 3 weeks for a least 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of carboplatin and pembrolizumab, participants with stable or responding disease receive pembrolizumab monotherapy on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Carboplatin; Biological: Trastuzumab

Arm B: Carboplatin Monotherapy

EXPERIMENTAL

Participants receive carboplatin on day 1. Patients who are HER2+ also receive trastuzumab IV every 3 weeks. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Participants with disease progression (PD) are eligible to receive pembrolizumab on day 1 of each cycle (crossover). Carboplatin may be continued or added back into the treatment regimen at the investigator's discretion. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Biological: Trastuzumab

Interventions

Pembrolizumab BIOLOGICAL

200 mg Given IV

Also known as: Keytruda

Arm A: Pembrolizumab + Carboplatin

Carboplatin DRUG

Arm A: area under the curve (AUC) 5 IV every 3 weeks Arm B: AUC 5 IV every 3 weeks

Also known as: Ribocarbo

Arm A: Pembrolizumab + Carboplatin; Arm B: Carboplatin Monotherapy

Trastuzumab BIOLOGICAL

For HER2+ patients: IV every 3 weeks using standard approved dosing

Also known as: Herceptin

Arm A: Pembrolizumab + Carboplatin; Arm B: Carboplatin Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced breast cancer with locally recurrent chest wall disease not amenable to surgical excision with curative intent.
• Distant sites of disease are allowed
• Prior radiation to the chest wall is not required
• The following disease subtypes are eligible:
• Triple negative disease (defined as ER \< 10%, PR \< 10%, HER2 negative)
• Hormone receptor positive, HER2 negative disease with evidence of progression on at least two prior lines of hormone therapy, unless, per treating investigator's judgement, is not considered a candidate for further endocrine therapy
• HER2 positive disease with evidence of disease progression on trastuzumab, pertuzumab, Trastuzumab emtansine (T-DM1), and oral tyrosine kinase inhibitor unless contraindicated with no other HER2 targeted therapy options available. Patients in this category will be classified by ER status
• Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) methodology using standard criteria.
• Cardiac function must be determined within 4 weeks of study entry to be \>= institutional lower limit of normal (LLN) using echo or multiple gated acquisition scan (MUGA).
• Any number of prior lines of therapy are allowed. a Prior platinum based therapy is allowed in the following settings:
• Treatment in the neoadjuvant and/or adjuvant setting without clear progression of disease.
• Treatment in the metastatic setting without clear progression of disease. b Neo/adjuvant treatment with a checkpoint inhibitor is allowed if the last treatment was at least 12 months from the diagnosis of metastatic disease.
• At least two weeks from last systemic therapy for breast cancer, with recovery of all treatment related toxicity to grade 1 or less. Subjects with \<= Grade 2 neuropathy are an exception to this criterion.
• At least two weeks from last radiation therapy, with recovery of all treatment related toxicity to grade 1 or less (excluding alopecia).
• Prior CNS disease is allowed if stable for at least one month since whole brain radiation therapy, and 2 weeks since stereotactic radiotherapy, and not requiring steroids. Patients whose CNS disease was surgically treated may be enrolled if stable for at least one month, and not requiring steroids.

You may not qualify if:

• Treatment with an investigational agent within 4 weeks of the first dose of treatment.
• Known active TB (Bacillus Tuberculosis). Patients with a distant history of tuberculosis that was appropriately treated and have no evidence of active infection are eligible to participate. Patients with a history of latent tuberculosis that was appropriately treated are also eligible to participate.
• Hypersensitivity to pembrolizumab or any of its excipients.
• Hypersensitivity to carboplatin or cisplatin
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/ interstitial lung disease
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Laura Huppert, MD, BA: lead
• Mayo Clinic: collaborator
• Johns Hopkins University: collaborator
• Translational Breast Cancer Research Consortium: collaborator
• Massachusetts General Hospital: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (9)

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• Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, Jungbluth A, Gnjatic S, Thompson JA, Yee C. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med. 2008 Jun 19;358(25):2698-703. doi: 10.1056/NEJMoa0800251.

  PMID: 18565862 BACKGROUND

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  PMID: 15771580 BACKGROUND

• Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T. PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13866-71. doi: 10.1073/pnas.231486598. Epub 2001 Nov 6.

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• Zhang X, Schwartz JC, Guo X, Bhatia S, Cao E, Lorenz M, Cammer M, Chen L, Zhang ZY, Edidin MA, Nathenson SG, Almo SC. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity. 2004 Mar;20(3):337-47. doi: 10.1016/s1074-7613(04)00051-2.

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• Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004 Jul 15;173(2):945-54. doi: 10.4049/jimmunol.173.2.945.

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• Sheppard KA, Fitz LJ, Lee JM, Benander C, George JA, Wooters J, Qiu Y, Jussif JM, Carter LL, Wood CR, Chaudhary D. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS Lett. 2004 Sep 10;574(1-3):37-41. doi: 10.1016/j.febslet.2004.07.083.

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  PMID: 19426218 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; Carboplatin; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Laura Huppert, MD
• Organization: University of California, San Francisco

Laura.Huppert@ucsf.edu

(415) 476-1000

Study Officials

• Laura Huppert, MD, BA

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Neelima Vidula, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: March 29, 2017
• Study Start: September 2, 2017
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: December 22, 2025
• Results First Posted: December 22, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)