Olinvacimab With Pembrolizumab in Patients With mTNBC
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|ClinicalTrials.gov Identifier: NCT04986852|
Recruitment Status : Recruiting
First Posted : August 3, 2021
Last Update Posted : August 17, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Metastatic Triple-Negative Breast Cancer||Drug: Olinvacimab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Patient will be assigned as sequentially with serial screening/ enrollment number.|
|Masking:||None (Open Label)|
|Masking Description:||It is open label study, so investigator and participant can know what is treated.|
|Official Title:||A Phase II, Open-Label, Multicenter Study of Olinvacimab in Combination With Pembrolizumab in Patients With Metastatic Triple-Negative Breast Cancer|
|Actual Study Start Date :||September 30, 2021|
|Estimated Primary Completion Date :||February 28, 2025|
|Estimated Study Completion Date :||August 30, 2026|
Experimental: Olinvacimab (TTAC-0001) 16 mg/kg and Pembrolizumab (Keytruda®) 200 mg
Treatment with Olinvacimab and Pembrolizumab is to be continued until disease progression, the development of unacceptable toxicity or patient's withdrawal of consent. Maximum duration of treatment will be 35 cycles (approximately 2 years).
Other Name: Pembrolizumab
- Objective response rate (ORR) [ Time Frame: Baseline upto 24 months ]ORR is defined as the proportion of subjects who achieve a best overall response (BOR) of complete response (CR) or partial response (PR). RECIST 1.1 will be used to determine ORR and patients with no post baseline tumor assessments, will be classified as non-responders
- Duration of response (DOR) [ Time Frame: Baseline upto 24 months ]DOR is defined as the time between the date of first response (CR or PR) according to RECIST 1.1 to the date of first disease progression, or death due to any cause, whichever occurs first.
- Disease control rate (DCR) [ Time Frame: Baseline upto 24 months ]DCR is defined as the proportion of subjects who achieve CR, PR, or stable disease (SD) according to RECIST 1.1.
- Progression-free survival (PFS) [ Time Frame: Baseline upto 24 months ]PFS time is defined as the time from the start date of the study drug administration to date of the first disease progression according to RECIST 1.1, or death due to any cause, whichever occurs first.
- Overall survival (OS) [ Time Frame: Baseline upto 24 months ]OS time is defined as the time from the start date of the study drug administration to the date of death due to any cause.
- ORR evaluated by iRECIST criteria: [ Time Frame: Baseline upto 24 months ]ORR will be evaluated based on iRECIST criteria in the FAS.
- DOR evaluated by iRECIST criteria: [ Time Frame: Baseline upto 24 months ]DOR will be evaluated based on iRECIST criteria in the FAS.
- DCR evaluated by iRECIST criteria: [ Time Frame: Baseline upto 24 months ]DCR will be evaluated based on iRECIST criteria in the FAS.
- PFS evaluated by iRECIST criteria: [ Time Frame: Baseline upto 24 months ]PFS will be evaluated based on iRECIST criteria in the FAS.
- OS evaluated by iRECIST criteria: [ Time Frame: Baseline upto 24 months ]OS will be evaluated based on iRECIST criteria in the FAS.
- Pharmacodynamic evaluation [ Time Frame: Baseline upto 24 months ]Change in concentration of serum biomarkers
- Exome sequencing of tumor tissue [ Time Frame: Screening visit ]The descriptive information of tumor tissue with mutation
- Immune suppression by level of circulating MDSC population [ Time Frame: Baseline upto 24 months ]The percent change of MDSC compared to baseline (before treatment on day 1 of cycle 1) will be measured.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||19 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Female patients ≥19 years old
Histologically proven metastatic triple-negative breast cancer* irrespective of PD-L1 status.
*Histological or cytological diagnosis of relapsed/metastatic triple receptor negative breast cancer (TNBC).TNBC is defined negatively expression of estrogen(ER), progesterone(PR) and human epidermal receptor-2(HER2). If there is a pathology report of the metastasis, take the histopathology of the metastases as standard. Negative of ER and PR is defined as expression of ER, PR<1% of the tumor cells by immunohistochemistry (IHC). HER2-negative is defined as a score of 0 and 1+ by IHC, or IHC 2+ & fluorescent in situ hybridization (FISH) negative. If the ER2 test result is 0 or 1+ by IHC, FISH detection is optional, but the result must be negative.
Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
- Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut
- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- Has received one or two prior lines of systemic therapy for metastatic or inoperable locally advanced TNBC
- No previous therapy with anti-VEGF, anti-VEGFR or anti-PD-1 antibody for their metastatic disease. The use of anti-VEGF, anti-VEGFR, anti-PD-1 or anti-PD-L1 antibody in neoadjuvant or adjuvant setting will be allowed if there was no progression of disease within 6 months after the completion of treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate hematologic, renal, and hepatic function tests performed within 7 days prior to initiation of study treatment
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Haemoglobin ≥ 9.0 g/dL (This must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin, e.g. ≥ approximately 3 months)
Blood coagulation tests
- Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (UNL)
- Activated partial thromboplastin time (aPTT) ≤ 1.5 x UNL
Hepatic function tests
- Total bilirubin ≤ 1.5 x UNL
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)
- Renal function test - Creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥30 mL/min for patient with creatinine levels >1.5 × institutional ULN 9) HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
- Participants on ART must have a CD4+ T-cell count 350 cells/mm3 at time of screening
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1) 10) 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 anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral 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 11) Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
- Note: Participants must have completed curative anti-viral 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 12) The patient should provide written informed consent
A patient who meets any of the following criteria is excluded from participating in this study.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
- Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 4 weeks prior to the baseline visit
- Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
- Not recovered below National Cancer Institute -Common Terminology Criteria for Adverse events (NCI-CTCAE v5.0) grade 1 or baseline from AEs due to previous therapy (patient with ≤ Grade 2 neuropathy or alopecia may be eligible)
- 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 the first dose of study drug
- Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed.
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) controlled by curative therapy are not excluded)
- Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic antibiotics
- HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
- Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.) or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. Treated depression with ongoing antidepressant medication is not an exclusion criterion
Female who is pregnant* or lactating and of childbearing potential who does not agree to a reliable and adequate method of contraceptiona A women of childbearing potential (WOCBP) must agree to use contraception during the treatment period and for at least 6 months (for females) after the last dose of study treatment.
aAdequate contraception allowed in this trial is as follows - Hormonal contraceptives such as combined oral contraceptive pill - Intrauterine devices or the implantation of intrauterine system (IUD)
- Blockage methods (spermicides and condoms/spermicides and [vaginal] diaphragm for contraception, vaginal sponges or cervical cap)
- Sterilization surgery such as tubal ligation in females *A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg) or seizure
- Class III or IV heart failure by New York Heart Association (NYHA) classification
- Requiring therapeutic anticoagulation treatment (prophylactic therapy with low-molecular weight heparin is allowed)
- Serious grade 4 venous thromboembolic event including pulmonary embolism
- Moderate to severe proteinuria as demonstrated by urine dipstick for proteinuria ≥2+. For patients with ≥2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined, or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible.
- History of abdominal fistula or gastrointestinal perforation, or serious GI bleeding within 6 months
- History of severe arterial thromboembolic event within 12 months of start of study drug
- Major surgery within 4 weeks prior to initiation of study treatment. (If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention).
- A known history of severe hypersensitivity (≥Grade 3) to study drugs and/or any of its excipients.
- Has had an allogenic tissue/solid organ transplant.
- Unable to participate in the trial according to the investigator's decision.
- Have received a live vaccine within 30 days prior to enrolment. Seasonal flu vaccines that do not contain live virus are permitted
- Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrolment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04986852
|Contact: Hyejin Leefirstname.lastname@example.org|
|Australia, Western Australia|
|Hollywood Private Hospital||Recruiting|
|Nedlands, Western Australia, Australia, 6009|
|Contact: Jeanette Devoto 61 8 6500 5555 email@example.com|
|Principal Investigator: Arlene Chan, MD, PhD|
|Principal Investigator:||Arlene Chan, Ph.D, MD||Hollywood Private Hospital, Australia|
|Principal Investigator:||Dhanusha Sabanathan, Ph.D, MD||Macquarie University, Australia|
|Principal Investigator:||Hong Shue, Ph.D, MD||University of Sunshine Coast, Australia|
|Principal Investigator:||Daphne Day, Ph.D, MD||Monash Medical Centre, Australia|
|Other Study ID Numbers:||
PMC_TTAC-0001_06 / KEYNOTE-C14
|First Posted:||August 3, 2021 Key Record Dates|
|Last Update Posted:||August 17, 2022|
|Last Verified:||August 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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