IRB Study Number 24-621
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
To compare MK-2870 plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to iDFS per investigator assessment
Secondary Objectives
To compare MK-2870 plus pembrolizumab to TPC with respect to OS
To evaluate MK-2870 plus pembrolizumab and TPC with respect to DRFS per investigator assessment
To evaluate MK-2870 plus pembrolizumab and TPC with respect to mean change from baseline in health-related QoL using the EORTC QLQ-C30 in all participants
To evaluate the safety and tolerability of MK-2870 plus pembrolizumab
Inclusion Criteria
Type of Participant and Disease Characteristics
Has centrally confirmed TNBC, as defined by the most recent ASCO/CAP guidelines. Note: TNBC status must be centrally confirmed prior to randomization. The biopsy specimen must come from the surgical resection that shows that the participant has non-pCR. Adequacy of a biopsy specimen for the above analyses must be confirmed by the central laboratory. Submission of another tumor specimen from the surgical resection may be required if adequate tumor tissue was not provided the first time.
Has no evidence of locoregional or distant relapse, as assessed by the treating physician.
Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to NCCN and/or local treatment guidelines for TNBC. Completed at least 5 doses of neoadjuvant pembrolizumab and chemotherapy, including at least one dose of anthracycline.
Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery.
Has non-pathologic complete response at surgery. pCR is defined as ypT0/Tis ypN0 (ie, no invasive residual disease in the breast or nodes; noninvasive breast residual disease is considered to be pCR in this definition.)
Is able to continue on adjuvant pembrolizumab.
Randomization must be conducted within 12 weeks from surgical resection.
Completed adjuvant radiation therapy (if indicated) and recovered before randomization.
Has provided tissue from the surgical resection for central laboratory determination of TROP2 status. Details pertaining to tumor tissue submission are provided in the Laboratory Manual.
Have LVEF of ≥50% or ≥institution LLN as assessed by ECHO or MUGA scan performed at screening.
Demographics
- Is an individual of any sex/gender, from at least 18 years of age inclusive, at the time of providing the informed consent.
Male Participants
- If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
MK-2870: 100 days after the final dose
Pembrolizumab: no requirements
Capecitabine: 95 days after the final dose
• Refrains from donating sperm PLUS either:
• Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
• Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below:
Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant PLUS partner use of an additional contraceptive method, as a condom may break or leak. Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use a penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
Female Participants
- A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a POCBP OR
• Is a POCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for each study intervention is:
◦ MK-2870: 190 days after the final dose
◦ Pembrolizumab: 120 days after the final dose
◦ Capecitabine: 185 days after the final dose
The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.6.
Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention.
Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
Informed Consent
- The participant has provided documented informed consent for the study. Note: Participants who are legally blind, unable to read, or have a mild developmental or intellectual disability and can indicate a wish to participate in this study may enroll if the eligibility criteria are met, a legally acceptable representative provides consent on their behalf, and an impartial witness participates in the consent process. If eligible, these participants may be enrolled in this study to allow the possibility of benefit from the planned treatment(s).
Additional Categories
Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia). Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible.
HIV-infected participants must have well controlled HIV on ART, defined as:
a. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening
b. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
c. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months
d. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study
e. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers) Note: A current list of FDA-approved strong/moderate inhibitors of CYP3A4 can be found at the above FDA website. This list is not all-inclusive. Any inhibitors not approved in the US will not appear in the list. The investigator should also refer to local approved product labels and use their best medical judgment.
Adequate organ function as defined in the following table (Table 6). Specimens must be collected within 7 days before the start of study intervention.
An ECOG performance status of 0 to 1 assessed within 7 days before first dose of study treatment.
Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
Hepatitis B screening tests are not required unless:
Known history of HBV infection
As mandated by local health authority
- Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative antiviral therapy at least 4 weeks prior to randomization.
Hepatitis C screening tests are not required unless:
Known history of HCV infection
As mandated by local health authority
Refer to Appendix 7 for country-specific requirements.
Exclusion Criteria
Medical Conditions
Has a known germline BRCA mutation (deleterious or suspected deleterious) and is eligible for adjuvant therapy with olaparib where olaparib is approved and available.
Has Grade >2 peripheral neuropathy.
History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea).
Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to study intervention.
Participants with uncontrolled systemic disease as judged by the investigator:
a. Participants with uncontrolled hypertension under medication intervention (systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg), history of unstable hypertension, or history of poorly compliant anti-hypertension treatment;
b. Participants with uncontrolled diabetes under medication intervention (fasting glucose ≥10 mmol/L and/or HbA1c ≥8%);
c. Participants with pleural effusion, pericardial effusion, or ascites that is clinically symptomatic or requires repeated drainage.
Prior/Concomitant Therapy
Received prior treatment with a TROP2-directed ADC or a topoisomerase I inhibitor containing ADC.
Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, PARP inhibitors, ADCs, and/or immunotherapy, with the exception of adjuvant radiation therapy.
Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period before starting MK-2870 is 2 weeks. Note: A list of strong inhibitors or inducers of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers Note: A current list of FDA-approved strong/moderate inhibitors of CYP3A4 can be found at the above FDA website. This list is not all-inclusive. Any inhibitors not approved in the US will not appear in the list. The investigator should also refer to local approved product labels and use their best medical judgment.
Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
Received prior radiotherapy within 3 weeks of start of study intervention, or required corticosteroids for radiation-related toxicities that cannot be discontinued before the first dose of study intervention. Note: Adjuvant radiation received as standard of care treatment for early-stage TNBC is permitted as long as there is at least 3 weeks between the last dose of radiation and the start of study intervention. Radiation related toxicities requiring corticosteroids must resolve before the first dose of study intervention.
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.5 for information on COVID-19 vaccines.
Prior/Concurrent Clinical Study Experience
- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
Diagnostic Assessments
Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
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 the first dose of study medication.
Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Active infection requiring systemic therapy.
HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. Refer to Appendix 7 for country-specific requirements.
Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Refer to Appendix 7 for country-specific requirements. Note: Hepatitis B and C screening tests are not required unless:
Known history of HBV and HCV infection
As mandated by local health authority
- History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual’s ability to cooperate with the requirements of the study, or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Other Exclusions
Severe hypersensitivity (Grade ≥3) to MK-2870, any of its excipients and/or to another biologic therapy.
History of allogeneic tissue/solid organ transplant.
Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
Severe hypersensitivity (Grade ≥3) to capecitabine and/or any of its excipients.
Participants who are incapacitated are not eligible for this study.
Refer to Appendix 7 for country-specific requirements.
