SWOG clinical trial number
S1418/BR006

A Randomized Phase III Trial to Evaluate Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer with >/=1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN1mi, ypN1-3) After Neoadjuvant Chemotherapy.

Open
Phase
Abbreviated Title
Rando Ph III of MK-3475 as adjuvant therapy for TNBC after neoadjuvant therapy
Status Notes
9/15/2020: Updated Funding Memo (Version Date 8/28/2020) includes a Non-Federal payment for TSH at Step 2 Randomization. This payment is effective for all patients that were registered to Step 2 regardless of date of registration.

BAHO substudy Partial Permanent Closure, Effective June 23, 2020 (Jan 28,2020) .

For English-speaking patients that were NOT registered to Step 2 (randomization) prior to the temporary closure of the BAHO substudy on January 28, 2020: The BAHO substudy questionnaire and blood sample submission (as indicated in Sections 15.2 and 15.3) are NOT required.

The BAHO substudy was limited to English-speaking patients only per Protocol Version date 07/30/2019.
An updated DTL was activated on 6/15/2018.

This study was activated 11/15/2016. The BAHO study was activated 1/15/17.

This is a potential FDA registration study. There is additional centralized and on-site monitoring conducted in addition to routine audits. Sites must also maintain a study specific Trial Master File for this study (https://www.swog.org/sites/default/files/docs/2017-10/Guidance%20on%20FDA%20Inspection.pdf).
Activated
11/15/2016
Participants
ALL NATIONAL CLINICAL TRIALS NETWORK MEMBERS

Research committees

Breast Cancer

Treatment

MK-3475

Other Study Materials

Eligibility Criteria Expand/Collapse

STEP 1
Pts must have histologically confirmed ER-, PR- and HER2-negative (triple-negative, TNBC) or ER, PR, and HER2 equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy. Pts who are HER2 positive by ASCO CAP guidelines are ineligible. HER2 negative and HER2 equivocal cases as per ASCO CAP guidelines, that do not receive HER2 targeted therapy are eligible. Pts with weekly ER or PR positive disease, defined as ER and/or PR <5% by immunohistochemistry, are eligible if the treating physician considers the patient not eligible for adjuvant endocrine therapy.

Residual disease must be >/= 1 cm in greatest dimension, and/or have positive lymph nodes (ypN+) on path exam.

Pts must not have metastatic disease.

Pts must not have locally recurrent disease.

It is preferred that axillary lymph node sampling is performed after completion of neoadjuvant chemo. Complete axillary lymph node dissection (ALND) after neoadjuvant chemotherapy is recommended in the following situations:

-Pts had documented path involvement of axillary nodes before neoadjuvant chemo and had sentinel node biopsy after neoadjuvant chemo with positive sentinel node(s).

-Pt had documented path involvement of the axillary nodes before neoadjuvant chemo and had only 1 sentinel lymph node removed after neoadjuvant chemo.

Except for (i) pts participating in A11202 trial or (ii) if the treating surgeon determines that a complete ALND is not in the best interest of the patient.

NOTE: Pts who undergo sentinel node biopsy before starting neoadjuvant treatment and do not undergo post neoadjuvant assessment of the axillary nodes or who have negative axillary nodes on post neoadjuvant assessment must have >/= 1 cm residual invasive cancer in the breast after completion of neoadjuvant chemo.

Pts must have a minimum of five, available unstained slides from the residual (post-neoadjuvant) invasive tumor in primary site or lymph node. These will be submitted to determine PD-L1 expression; tumor tissue must be adequate for PD-L1 testing, (minimum of 100 cancer cells per slide).

Pts must be offered the opportunity to participate in specimen banking.

Pts must have had neoadjuvant chemo followed by surgery. Pts who cannot complete all planned treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease. Pts must have resolution of AEs of the most recent prior chemo to </=Grade 1 (except alopecia and </= Grade 2 neuropathy).

Pts may receive post-op chemo for up to 24 weeks after completion of surgery. Pts must have resolution of AEs of the most recent prior chemotherapy to </=Grade 1 (except alopecia and </= Grade 2 neuropath). Adjuvant chemo must have been completed within 35 days prior to screening registration and must be given prior to radiation.

Pts must have completed their final breast surgery (rendering them free from disease) with clear resection margins for invasive cancer and DCIS within 90 days prior to screening reg for patients not receiving post-op chemo, or within 270 days prior to screening reg for patients who have completed post-op chemotherapy.

Pts who receive postoperative chemotherapy may receive radiation therapy before or after the chemotherapy. A short course of reduced dose chemotherapy concomitant with radiation for radiation sensitization is not considered to be adjuvant chemotherapy. Positive margins are allowed only if the surgical team of the patient deems further resection impossible.

Pts for whom RT to the affected breast or chest wall and regional nodal areas is clinically indicated (per NCCN) should receive RT after randomization when possible, and receive MK-3475 concurrent with RT, if randomized to the experimental arm. However, RT administered prior to reg is also allowed. Pembrolizumab may be added to ongoing radiation, or started after its completion, if randomized to the experimental arm, provided there are no > Grade 2 radiation-related skin toxicities. Pts who have not yet started radiation must specify at the time of screening registrations whether or not they will receive RT and the extent of the intended RT.

Pts must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti- CTLA4 or similar drugs. Pts must not be planning to receive any of the prohibited therapies listed in Section 7.3 during the screening or treatment phases of the study.

Pts must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol.

Pts must be women or men >/= 18 years of age.

Pts must have Zubrod PS </= 2.

Pts must not have a history of (non- infectious) pneumonitis that required steroids or evidence of active pneumonitis.

Pts must not have an active infection requiring systemic therapy.

Pts must not have active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment.

Pts must not have received live vaccines within 30 days prior to reg. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines, and are not allowed.

Pts must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection prior to reg. Pts who have completed curative therapy for HCV are eligible. Patients with known HIV infection are eligible if they meet each of the following 3 criteria:
- CD4 counts >/= 350 mm3
- Serum HIV viral load of < 25,000 IU/ml and
-Treated on a stable antiretroviral regimen.

No other prior invasive malignancy is allowed except for the following: adequately treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer. Stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years.

Pts must have complete history and physical examination withing 28 days prior to registration.

Pts must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines.

As a part of the OPEN reg process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

STEP 2 REGISTRATION (Randomization)
Pts must not be registered to Step 2 until receiving confirmation from the SWOG Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing. Pts must be registered within 7 days of receiving the e-mail notification confirming submission was evaluable for PD-L1 status.

A serum TSH must be obtained within 28 days prior to Step 2 reg to obtain a baseline value.

Pts must have adequate bone marrow function as evidenced by all of the following: ANC >/= 1,500/mcL; platelets >/= 100,000/mcL; Hemoglobin >/= 9 g/dL. These results must be obtained within 28 days prior to Step 2 reg.

Pts must have adequate hepatic function as evidenced by the following: total bilirubin </= 1.5 x IULN (except Gilberts Syndrome, who must have a total bilirubin < 3.0 mg/dL), and AST or ALT and alkaline phosphatase </= 2.5 x IULN. These results must be obtained within 28 days prior to Step 2 reg.

Pts must have adequate renal function as evidenced by ONE of the following: serum creatinine </= IULN OR measured or calculated creatinine clearance >/= 60 mL/min. This result must have been obtained within 28 days prior to Step 2 reg..
WCBP must have a negative urine or serum pregnancy test within 28 day prior to reg.

Women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication. Pts must not be pregnant or nursing due to unknown teratogenic side effects.

Site must verify that there is no known change in the Step 1 eligibility since initial reg.