This clinical study is an open-label, Phase 1, dose-escalation study to determine the safety, tolerability, and efficacy of the drug product produced by Administering CRX100 alone and in combination with Pembrolizumab in advanced solid malignancies. Patients will be screened and evaluated to determine whether or not they meet stated inclusion criteria. Enrolled subjects will undergo leukapheresis to enable the ex vivo generation of CRX100. Patients with non-small cell lung cancer (NSCLC), ovarian cancer, colorectal cancer, hepatocellular carcinoma (HCC), malignant melanoma (excluding uveal melanoma), gastric cancer, triple negative breast cancer, and osteosarcoma.
The study will start with monotherapy dose escalation followed by combination cohorts.
Age ≥18 years at the time of consent.
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).
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.
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.
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.
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.
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.
Subjects who received any type of cell-based therapies within the last 12 weeks from the planned apheresis date.
Sequential
CRX100 suspension for infusion
Biological/VaccineA fixed dose of CIK cells combined with the specified dose of CDSR.
Fludarabine
Combination product25mg/m IV (five doses given from Day -7 until Day -3)
Cyclophosphamide
Combination product60mg/kg intravenous (IV) (two doses given on Day -7 and -6)
Frequency of treatment-emergent Adverse Events and Dose Limiting Toxicities
The Primary Outcome Measure will be based on the frequency of treatment-emergent Adverse Events and Dose Limiting Toxicities during and after the administration of investigational drug in monotherapy and investigational drug with combination therapy.
Determine the maximum tolerated dose (MTD), maximum feasible dose (MFD) or optimal biological dose (OBD) and determine recommended Phase 1b/Phase 2a dose level.
Review of safety review committee following subject treatment to review any AEs, SAEs, or DLTs
Biodistribution of CRX100 based on subject's viral load as assessed through a viral shedding assay.
To characterize the biodistribution of CRX100 based on each subject's viral load as assessed through a viral shedding assay, following a single dose of investigational product.
Immune response to investigational drug based on subject's levels of neutralizing antibodies.
Levels of neutralizing vvDD antibodies will be summarized by dose level and time point following a single dose of investigational product.
Early anti-tumor activity of investigational drug based on iRECIST criteria
Summarized based on best response observed using RECIST classification of response. Overall response and frequencies of each level of response.
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