Study of CRX100 as Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Solid Malignancies
NCT ID: NCT04282044
Last Updated: 2024-02-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
60 participants
INTERVENTIONAL
2021-01-08
2026-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The study will start with monotherapy dose escalation followed by combination cohorts.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies
NCT02419495
A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies
NCT00441337
A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors
NCT02009449
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
NCT04198766
Study of AMV564 in Subjects With Advanced Solid Tumors
NCT04128423
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Monotherapy Dose-Escalation Cohorts
Prior to the current amendment, no DLTs were observed at Dose Levels 1-5. Starting with the current protocol amendment, dosing decisions in monotherapy cohorts will utilize a 3+3 design for Dose Level 6. CRX100 infusion will occur every nine weeks (+/- 7 days). Subjects will receive up to a maximum of four infusions of CRX100 unless it is determined by the treating physician and the sponsor that it is in the best interest of the subjects to receive additional doses of CRX100 beyond four doses. A minimum of three DLT-evaluable subjects will be doses at Dose Level 6 and expanded to six subjects if determined necessary based on DLT incidence using the 3+3 design, and discussion with SRC and Sponsor.
CRX100 suspension for infusion
A fixed dose of CIK cells combined with the specified dose of CDSR.
Fludarabine
25mg/m IV (five doses given from Day -7 until Day -3)
Cyclophosphamide
60mg/kg intravenous (IV) (two doses given on Day -7 and -6)
Combination Therapy Cohorts
Subjects with relasped or refractory solid tumors, as defined in the inclusion criteria, will be enrolled to evaluate the safety and anti-tumor activity of CRX100 in combination with Pembrolizumab in patients with advanced solid malignancies. The dose of CRX100 used will be determined from the monotherapy cohorts.
CRX100 infusion will occur every nine weeks (+/- 7 days). Subjects will receive up to a maximum of four doses of CRX100 unless it is determined by the treating physician and the sponsor that it is in the best interest of the subjects to receive additional doses of CRX100 beyond four doses.
Pembrolizumab will be administered at 200mg IV every three weeks (Q3W) per the approved label.
CRX100 suspension for infusion
A fixed dose of CIK cells combined with the specified dose of CDSR.
Fludarabine
25mg/m IV (five doses given from Day -7 until Day -3)
Cyclophosphamide
60mg/kg intravenous (IV) (two doses given on Day -7 and -6)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
CRX100 suspension for infusion
A fixed dose of CIK cells combined with the specified dose of CDSR.
Fludarabine
25mg/m IV (five doses given from Day -7 until Day -3)
Cyclophosphamide
60mg/kg intravenous (IV) (two doses given on Day -7 and -6)
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Age ≥18 years at the time of consent.
2. Written informed consent in accordance with national, local, and institutional guidelines obtained prior to any study procedures. (Screening assessments performed prior to informed consent but within the 28-day screening window are acceptable for inclusion purposes).
3. Subjects must have histologically confirmed diagnosis of one of the following tumors: triple negative adenocarcinoma of the breast (human epidermal growth factor receptor 2 negative, estrogen receptor negative and progesterone receptor negative \[HER2-/ER-/PR-\]), adenocarcinoma of the colon or rectum, hepatocellular carcinoma (HCC), osteosarcoma, epithelial ovarian cancer, malignant melanoma, non-small cell lung cancer (NSCLC), or gastric cancer. Documentation of the diagnosis with the original pathology report, or a recent biopsy, is required.
4. Subjects must have relapsed disease or refractory disease. Subjects must have received, completed, or become intolerant of prior standard of care therapies or are not expected to derive any clinical benefit from standard of care therapies.
5. Subjects with Ovarian cancer must have received at least one prior standard of care for their relapsed or refractory disease, which must include a platinum-based regimen.
6. Subjects agree to provide fresh tumor tissue that has not been previously irradiated. If biopsy procedure is not safe to perform, then archival tumor tissue (20 slides or a tissue block) can be submitted.
7. Subjects must have iRECIST evaluable disease using computed tomography (CT) or magnetic resonance imaging (MRI) with IV contrast, with at least one measurable target lesion.
8. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
9. Subjects are expected to have a life expectancy of at least 12 weeks from the time of enrollment.
10. Adequate hematologic function at the time of screening, defined as: absolute lymphocyte count (ALC) \>500 cells/mm3, absolute neutrophil count (ANC) \>750 cells/mm3, hemoglobin \>8 g/dL, and platelet count \>50,000 cells/mm3. For subjects enrolling into the LDC cohorts, the criteria are defined as: ALC\>500 cells/mm3, ANC\>1000 cells/mm3, hemoglobin\>8g/dL, and platelet count\>100,000 cells/mm3.
a. Hemoglobin and platelet count thresholds must be achievable without transfusion of red blood cells or platelets, or use of growth factors administered within two weeks.
11. Adequate organ function, defined as:
1. Renal function: serum creatinine \<1.5x institutional upper limit of normal (ULN) or calculated creatinine clearance \>50 mL/min.
2. Adequate hepatic function: total bilirubin ≤1.5x institutional ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x institutional ULN, unless liver metastases are present, in which case it must be ≤5x ULN; International Normalized Ratio (INR) ≤1.5. For subjects with HCC, adequate hepatic function is defined as: total bilirubin ≤3x institutional upper limit of normal, AST/ALT ≤5x institutional ULN, INR ≤1.7, Child-Turcotte-Pugh score \<8.
12. Women of childbearing potential (defined as all subjects physiologically capable of becoming pregnant) must have negative serum ß-human chorionic gonadotropin (hCG) or urine pregnancy test.
13. Women of childbearing potential must agree to use highly effective methods of contraception throughout the study and for six months after the last dose of CRX100.
14. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method throughout the study and for six months after the last dose of CRX100.
15. Subjects must be willing and able to comply with all study procedures, requirements, and follow-up examinations.
Exclusion Criteria
1. Subjects with new or progressive brain metastasis. Subjects with treated brain metastases are eligible if there is no evidence of progression for at least four weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
2. Subjects who received any chemotherapy or immunotherapies (non-cell-based therapies) or oncolytic virus therapy, radiotherapy, radiosurgery or investigational agents within three weeks of enrollment.
3. Subjects who still are experiencing Grade 2 or higher AEs from prior therapies such as surgery, radiation therapy and systemic anti-cancer therapies unless approved by sponsor.
4. Subjects who received any type of cell-based therapies within the last 12 weeks from the planned apheresis date.
5. Subjects experiencing any active infections (bacterial, viral, or fungal) for which systemic antimicrobials are required. Subjects who need prophylactic anti-viral agents that can inhibit the replication of VACV will be excluded from participating.
6. Subjects must not have history of active or symptomatic autoimmune disease or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, other symptomatic autoimmune disease, documented history of autoimmune disease or syndrome requiring systemic treatment in the past two years (i.e., with use of disease modifying agents, steroids or immunosuppressive agents) Exceptions are permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, conditions not expected to recur in the absence of an external trigger or other conditions approved by the medical monitor.
7. Have a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to apheresis, and within 14 days prior to infusion. Inhaled, intramuscular injection, or topical steroids and adrenal replacement doses (≤10 mg daily prednisone equivalents) are permitted. Stable doses of steroids are permitted for subjects with pre-treated brain metastases. Short-term (\<48 hr) steroid pretreatment for contrast allergy for imaging is permitted.
8. Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illnesses unrelated to cancer, or any serious medical or psychiatric illness that could, in the Investigator's opinion, interfere with participation in this study.
9. Pregnant or nursing an infant (subject or household contacts).
10. Clinically significant immunodeficiency (e.g., due to underlying illness and/or medication) in a subject or household contacts.
11. Have any underlying medical condition (including, but not limited to, ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia), psychiatric condition that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs.
12. Have a history of another invasive malignancy, except for the following circumstance: individuals with a history of invasive malignancy are eligible if they have been disease free and off treatment for at least two years or are deemed by the Investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if diagnosed and treated: carcinoma in situ of the breast, oral cavity, or cervix, localized prostate cancer, or basal cell or squamous cell carcinoma of the skin. When enrolling a subject with another malignancy, the Investigator must discuss the subject with the Medical Monitor.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
BioEclipse Therapeutics
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Oliver Dorigo, MD
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
HonorHealth Research Institute
Scottsdale, Arizona, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Stanford University
Stanford, California, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CRX100-001
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.