A phase II study of Pembrolizumab plus Carboplatin in BRCA-related metastatic breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Nov 2018 → ongoing

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MSD ITALIA

External identifiers

EU CT number

2024-515686-34-00

EudraCT number

2016-001314-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The ORR (complete response plus partial response) will be evaluated according to RECIST v1.1 criteria

Secondary objectives 2

1. TTP will be calculated as the time between the enrolment and the disease progression. The duration of response (DOR) will be measured from the time of the first ORR is recorded to the date of progression is objectively documented. The Disease Control Rate (DCR) will be evaluated as the percentage of patients with ORR and stable disease. OS will be considered as the interval between the enrolment and the death or the last date the patient was alive.
2. Safety: The safety of the combination will be evaluated according to the worst toxicity grade reported throughout the whole treatment period.

Conditions and MedDRA coding

BRCA-related metastatic breast cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be >=18 years of age on day of signing informed consent. 3. Patients must have metastatic confirmed breast cancer 4. Disease progression by radiological techniques within 12 months prior to signing informed consent 5. Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (unknown significance variants) 6. Presence of at least 1 measurable lesion based on RECIST v1.1. 7. Prior chemotherapy with anthracyclines and taxanes has to be administered. 8. No more than one line of chemotherapy for advanced disease has to be administered 9. In case of luminal tumors hormonal treatments for advanced disease can be administered before 10. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen 11. Have a performance status of 0 or 1 on the ECOG Performance Scale. 12. Life expectancy of greater than 3 months 13. Demonstrate adequate organ function as defined. All screening labs should be performed within 10 days of treatment initiation.

Exclusion criteria 1

1. 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has a benign variant of BRCA1/2 genes 3. Has received more than one line of chemotherapy for advanced disease 4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 5. Has a known history of active TB (Bacillus Tuberculosis) 6. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 7. Has had an allogenic tissue/solid organ transplant 8. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 9. 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 and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 10. 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. 11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 12. 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 13. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 14. Has an active infection requiring systemic therapy. 15. 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. 16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 17. Has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Is exclude also women pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The objective response rate

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Laura Cortesi

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Laura Cortesi

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications