Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: GV20 Therapeutics
Must not be taking: Steroids, Immunosuppressives, PD-1 modulators
Disqualifiers: Heart disease, Active infections, Autoimmune, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase 1/2A study of GV20-0251 being developed for the treatment of participants with advanced solid tumors, who are refractory to approved therapies or other standard of care.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any investigational agents or anticancer treatments within 2 weeks before starting the study medication.
What safety data exists for the treatment GV20-0251 in humans?
The treatment, also known as G207, has been tested in humans with malignant gliomas, and no serious side effects directly linked to the treatment were found. Some patients experienced mild symptoms like fever, but these were manageable and resolved with standard care. Overall, the treatment appears to be safe for use in humans.
12345What makes the drug GV20-0251 unique for cancer treatment?
GV20-0251 is unique because it involves the granulocyte colony-stimulating factor (G-CSF), which is known to promote tumor growth and angiogenesis (formation of new blood vessels) in certain cancers. This suggests that GV20-0251 may target the G-CSF/G-CSFR signaling pathway, which is associated with cancer cell survival and growth, making it a novel approach compared to standard treatments.
678910Eligibility Criteria
This trial is for adults with advanced solid tumors that have not responded to standard treatments. They should be expected to live at least 12 weeks, have certain lab results within specific ranges, and no active severe diseases or infections. Participants must not have had recent cancer therapies or investigational drugs and agree to use contraception.Participant Groups
The study tests GV20-0251 in patients with solid tumor malignancies that are resistant to current therapies. It's a Phase 1 trial focusing on the safety and effectiveness of this new potential treatment option for those who've exhausted approved treatments.
4Treatment groups
Experimental Treatment
Group I: Part D - GV20-0251 in Combination with Pembrolizumab Dose Expansion in up to 5 indicationsExperimental Treatment1 Intervention
The BOP2 will be applied to further characterize the anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 in combination with pembrolizumab at the preliminary RP2D in up to 5 expansion cohorts involving eligible participants.
Group II: Part C - GV20-0251 in Combination with Pembrolizumab Dose Escalation in 2-4 dose levelsExperimental Treatment1 Intervention
The Bayesian optimal interval (BOIN) design will be employed to evaluate the safety and tolerability of GV20-0251 in combination with pembrolizumab, and to determine the MTD or the preliminary RP2D of this combination in selected tumor indications.
Group III: Part B - Multiple Expansion Cohorts in up to 4 tumor indicationsExperimental Treatment1 Intervention
The Bayesian optimal design for Phase II (BOP2) will be utilized to further characterize the anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 at the preliminary RP2D in up to 4 expansion cohorts involving eligible participants.
Group IV: Part A - Dose Escalation in up to 7 dose levelsExperimental Treatment1 Intervention
A 3+3 dose escalation scheme will be used to evaluate the safety and tolerability of GV20-0251, and to establish the maximum tolerated dose (MTD) or the preliminary recommended Phase 2 dose (RP2D).
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Florida Cancer Specialists & Research Institute, LLCFort Myers, FL
HealthONE Clinic Services Oncology - Hematology, LLC d/b/a Sarah Cannon Research Institute at HealthONEDenver, CO
Community Health Network, Inc.Indianapolis, IN
More Trial Locations
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Who is running the clinical trial?
GV20 TherapeuticsLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. [2023]G207 is a conditionally replicating derivative of herpes simplex virus (HSV) type-1 strain F engineered with deletions of both gamma(1)34.5 loci and a lacZ insertion disabling the UL39 gene. We have demonstrated the efficacy of G207 in treating malignant glial tumors in athymic mice, as well as the safety of intracerebral G207 inoculation in mice and in Aotus nancymai. We sought to determine the safety of G207 inoculation into cerebral malignant glial tumors in humans. Criteria for inclusion into this dose-escalation study were the diagnosis of histologically proven malignant glioma, Karnofsky score > or = 70, recurrence despite surgery and radiation therapy, and an enhancing lesion greater than 1 cm in diameter. Serial magnetic resonance images were obtained for volumetric analysis. The trial commenced at a dose of 10(6) plaque forming units (p.f.u.) inoculated at a single enhancing site and was completed when the 21st patient was inoculated with 3x10(9) p.f.u. at five sites. While adverse events were noted in some patients, no toxicity or serious adverse events could unequivocally be ascribed to G207. No patient developed HSV encephalitis. We found radiographic and neuropathologic evidence suggestive of anti-tumor activity and long-term presence of viral DNA in some cases.
A Comparative Safety Profile Assessment of Oncolytic Virus Therapy Based on Clinical Trials. [2022]Oncolytic virus therapy (OVT) represents a new class of therapeutic agents in cancer treatment. The molecular and cellular mechanisms of action of OVTs have been evaluated in nonclinical/clinical phase trials. Various genetically modified viruses have been developed as oncolytic agents, and the first approval of an OVT for clinical use was issued by the US Food and Drug Administration in 2015. In this context, more and more clinical development of OVTs is anticipated in the future. This article provides a risk assessment of OVT based on the safety data obtained from all clinical trials to date using a publicly available database. The most common adverse events (AEs) observed in clinical trials have been infection-related symptoms such as fatigue, chills, fever, and nausea; few serious AEs have been observed, regardless of the kind of virus or transfected genes. In vivo systemic infusion of OVTs demonstrated a high percentage of AEs, but most AEs were manageable using common drugs. This paper describes OVTs' specific safety/toxicity profiles and encourages the performance of further clinical trials of OVTs to address the most serious challenges anticipated in the development of OVTs as a new class of drugs for the treatment of cancer.
Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. [2023]We have previously demonstrated safety of G207, a doubly mutated (deletion of both gamma(1)34.5 loci, insertional inactivation of U(L)39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score >or=70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 x 10(9) plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity.
The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers. [2020]Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev-C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.
Clinical landscape of oncolytic virus research in 2020. [2021]Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed search identified 119 papers from 2000 to 2020 with 97 studies reporting data on 3233 patients. The viruses used, presence of genetic modifications and/or transgene expression, cancer types targeted, inclusion of combination strategies and safety profile were reported. In addition, information on viral bioshedding across the studies, including which tissues or body fluids were evaluated and how virus was detected (eg, PCR, plaque assay or both), is also reported. Finally, the number of studies evaluating antiviral and antitumor humoral and cellular immune responses were noted. We found that adenovirus (n=30) is the most common OV in clinical trials with approximately two-thirds (n=63) using modified or recombinant viral backbones and granulocyte-macrophage colony-stimulating factor (n=24) was the most common transgene. The most common tumors targeted were melanoma (n=1000) and gastrointestinal (GI; n=577) cancers with most using monotherapy OVs given by intratumoral (n=1482) or intravenous (n=1347) delivery. The most common combination included chemotherapy (n=36). Overall, OV treatment-related adverse events were low-grade constitutional and local injection site reactions. Viral shedding was frequently measured although many studies restricted this to blood and tumor tissue and used PCR only. While most studies did report antiviral antibody titers (n=63), only a minority of studies reported viral-specific T cell responses (n=10). Tumor immunity was reported in 48 studies and largely relied on general measures of immune activation (eg, tumor biopsy immunohistochemistry (n=25) and serum cytokine measurement (n=19)) with few evaluating tumor-specific immune responses (n=7). Objective responses were reported in 292 (9%) patients and disease control was achieved in 681 (21.1%) patients, although standard reporting criteria were only used in 53% of the trials. Completed clinical trials not reported in the peer-reviewed literature were not included in this review potentially underestimating the impact of OV treatment. These data provide insight into the current profile of OV clinical trials reporting and identifies potential gaps where further studies are needed to better define the role of OVs, alone and in combination, for patients with cancer.
G-CSF receptor expression in ovarian cancer. [2019]Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is clinically used to overcome neutropenic periods during chemotherapy. In vitro studies using cell lines as a model system have recently suggested that G-CSF can promote ovarian cancer growth. The objective of this work is to determine whether tumor cells express G-CSF-receptors (G-CSFR). A set of ovarian tumor biopsies and ovarian cancer cell lines was analyzed by RT-PCR, immunohistochemistry and immunofluorescence. The presence of a 276 bp-amplicon (exon 8-10) obtained by RT-PCR showed that 12 out of 16 ovarian tumor biopsies and two out of four ovarian cancer cell lines expressed G-CSFR-mRNA. G-CSFR-protein was detected in tumor cells of the 12 biopsies that also contained G-CSFR-mRNA. A second 409 bp-amplicon (exon 17) obtained by RT-PCR from the variable C-terminal cytoplasmic region of G-CSFR could be amplified only in four out of 16 biopsies and in none of the ovarian cancer cell lines studied. The results presented here indicate that G-CSFR is frequently expressed in ovarian cancer cells. Moreover, the failure of RT-PCR amplification of the 409 bp-amplicon in samples that express G-CSFR-mRNA suggests that C-terminal truncated receptor forms are also expressed.
Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer. [2019]In attempt to develop a new chemotherapeutic regimen including carboplatin (CBDCA), epirubicin (EPI), and VP-16 in extensive small cell lung cancer, with a higher dose intensity compared with previous experience of our group, we determined the maximum tolerated dose (MTD) of VP-16 when administered in association with CBDCA (300 mg/ m2, i.v., day 1) and EPI (75 mg/m2, i.v., day 1), recycling chemotherapy every 3 weeks, with the support of granulocyte-colony-stimulating factor (G-CSF). A total of 15 patients received three dose levels of VP-16 (mg/m2, i.v., daily on days 1-3): 100 (three patients), 120 (six), and 140 (six). G-CSF was administered subcutaneously at the dose of 5 micrograms/kg/day on days 6-15 of each chemotherapy course. The MTD was established at 140 mg/m2 and myelotoxicity, grade 4 neutropenia with death for sepsis in one case and grade 3 thrombocytopenia in three cases, was dose limiting. The recommended dose of VP-16 for a phase II study is 140 mg/m2.
Intermittent granulocyte colony-stimulating factor maintains dose intensity after ABVD therapy complicated by neutropenia. [2013]Granulocyte Colony-Stimulating Factor (G-CSF) is commonly used to maintain dose intensity in patients receiving ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) for Hodgkin lymphoma. However, the need for growth factor support is unclear, with studies suggesting that dose intensity can be maintained without G-CSF. Moreover, G-CSF is expensive (pegfilgrastim: EUR 1540/cycle; 300 μg filgrastim for 7 days: EUR 700/cycle) and is associated with side effects including bone pain and increased risk of bleomycin lung toxicity. Intermittent G-CSF may be an effective compromise, given that the effect of G-CSF on granulocyte precursors in vitro persists for 4-5 days after administration. After promising results of a pilot study, this schedule has been used subsequently in the majority of our patients receiving G-CSF as secondary prophylaxis for ABVD complicated by neutropenia.
Granulocyte colony-stimulating factor/granulocyte colony-stimulating factor receptor biological axis promotes survival and growth of bladder cancer cells. [2007]A significant fraction of invasive bladder carcinomas express both granulocyte colony-stimulating factor (G-CSF) and granulocyte colony-stimulating factor receptor (G-CSFR). We sought to determine whether G-CSF/G-CSFR signaling promotes survival and growth of bladder cancer cells. The bladder carcinoma cell line 5637 constitutively secretes G-CSF but lacks G-CSFR expression. In contrast, TCC-SUP lacks expression of both G-CSF and G-CSFR. Using these bladder cancer cell lines as our model systems, we studied the effects of G-CSFR expression on cell proliferation, survival, and growth in vivo.
Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor Survival. [2019]BACKGROUND Chemotherapy for advanced gastric cancer (GC) patients has been the mainstay of therapy for many years. Although adding anti-angiogenic drugs to chemotherapy improves patient survival slightly, identifying anti-angiogenic therapy-sensitive patients remains challenging for oncologists. Granulocyte colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient survival remain unclear. MATERIAL AND METHODS Seventy GC tissue samples were collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40 paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical characteristics, VEGF-A levels and overall survival were analyzed. Biological function and underlying mechanistic investigations were carried out using SGC7901 cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube formation were examined. RESULTS The levels of G-CSFR were upregulated in GC tissues compared to normal mucosa tissues. Higher G-CSF expression was associated with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas higher G-CSFR expression was associated with lymph node metastasis. Patients with higher G-CSF expression had shorter overall survival times. In vitro, G-CSF stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and accelerated HUVEC tube formation. CONCLUSIONS These data suggest that increased G-CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by stimulating tumor proliferation, migration, and angiogenesis, indicating that these factors are potential tumor targets for cancer treatment.