GV20-0251 for Cancer

Recruiting at 12 trial locations

Overseen By GV20 Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GV20 Therapeutics

Must not be taking: Steroids, Immunosuppressives, PD-1 modulators

Disqualifiers: Heart disease, Active infections, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

365 Participants Needed

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. ^{1 2 3 4 5}

What 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. ^{6 7 8 9 10}

Eligibility 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.

Inclusion Criteria

Life expectancy of >=12 weeks

I have been cancer-free from any second cancer for at least 2 years.

I have one or more tumors that can be measured for treatment response.

Exclusion Criteria

I have been diagnosed with HIV, Hepatitis B, or Hepatitis C.

I am on long-term steroids or immunosuppressants for an autoimmune disease or other condition.

I have symptoms from a brain tumor or cancer spread to the brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A - Dose Escalation

A 3+3 dose escalation scheme to evaluate the safety and tolerability of GV20-0251 and establish the maximum tolerated dose or preliminary recommended Phase 2 dose

12 months

Part B - Multiple Expansion Cohorts

Bayesian optimal design for Phase II to characterize anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 at the preliminary RP2D

12 months

Part C - Combination Dose Escalation

Bayesian optimal interval design to evaluate the safety and tolerability of GV20-0251 in combination with Pembrolizumab and determine the MTD or preliminary RP2D

12 months

Part D - Combination Dose Expansion

BOP2 applied to further characterize anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 in combination with Pembrolizumab at the preliminary RP2D

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• GV20-0251

Trial Overview 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.

Participant Groups

Group I: Part D - GV20-0251 in Combination with Pembrolizumab Dose Expansion in up to 5 indications Experimental Treatment 1 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 levels Experimental Treatment 1 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 indications Experimental Treatment 1 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 levels Experimental Treatment 1 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).

Who Is Running the Clinical Trial?

GV20 Therapeutics

Lead Sponsor

Trials

1

Recruited

370+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

G207, a modified herpes simplex virus, was safely administered to 21 patients with malignant gliomas, with doses escalating from 10^6 to 3x10^9 plaque forming units, and no serious adverse events linked to the treatment were observed.

The study provided early evidence of anti-tumor activity, as indicated by radiographic and neuropathologic findings, along with the long-term presence of viral DNA in some patients, suggesting potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Markert, JM., Medlock, MD., Rabkin, SD., et al.[2023]

Oncolytic virus therapy (OVT) has been recognized as a promising cancer treatment, with the first OVT approved by the FDA in 2015, indicating its potential efficacy in clinical settings.

The safety profile of OVTs shows that while common adverse events like fatigue and fever are frequent, serious adverse events are rare and manageable, suggesting a favorable safety margin for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Safety Profile Assessment of Oncolytic Virus Therapy Based on Clinical Trials. Matsuda, T., Karube, H., Aruga, A.[2022]

G207, a modified herpes simplex virus, has been shown to be safe for patients with recurrent malignant gliomas when administered in two doses before and after tumor resection, with no severe adverse effects reported.

Preliminary evidence suggests that G207 may have antitumor activity, as indicated by radiographic and neuropathologic findings, and it demonstrated viral replication in the treated areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Markert, JM., Liechty, PG., Wang, W., et al.[2023]

Oncolytic viral therapy, particularly talimogene laherparepvec (T-VEC), has been established as a standard treatment for melanoma since its FDA approval in 2015, with ongoing development of other oncolytic viruses like HF10 and CVA21 in clinical trials.

While oncolytic viruses have shown safety and promising efficacy in glioma and in combination with other treatments for breast cancer, their effectiveness as monotherapies, especially for pancreatic cancer, remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers. Eissa, IR., Bustos-Villalobos, I., Ichinose, T., et al.[2020]

Oncolytic viruses (OVs) are being tested in clinical trials for cancer treatment, with adenovirus being the most commonly used, and most trials focusing on melanoma and gastrointestinal cancers, showing low-grade adverse events.

Out of 3233 patients studied, only 9% had objective responses to OV treatment, but 21.1% achieved disease control, indicating that while OVs show promise, more research is needed to fully understand their efficacy and immune response mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical landscape of oncolytic virus research in 2020. Macedo, N., Miller, DM., Haq, R., et al.[2021]

A significant number of ovarian tumor biopsies (12 out of 16) and some ovarian cancer cell lines (2 out of 4) were found to express G-CSF receptors (G-CSFR), indicating that these tumors may respond to G-CSF.

The study suggests that ovarian cancer cells may express truncated forms of the G-CSFR, as indicated by the failure to amplify a specific receptor segment in most samples, which could have implications for understanding how G-CSF influences ovarian cancer growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

G-CSF receptor expression in ovarian cancer. Ninci, EB., Brandstetter, T., Meinhold-Heerlein, I., et al.[2019]

The maximum tolerated dose (MTD) of VP-16 in combination with carboplatin and epirubicin for treating extensive small cell lung cancer was determined to be 140 mg/m2, based on a study involving 15 patients.

The study highlighted significant myelotoxicity as a dose-limiting factor, with one patient experiencing grade 4 neutropenia leading to death from sepsis, indicating the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer. Gridelli, C., D'Aprile, M., Palmeri, S., et al.[2019]

A study involving 85 patients and 848 chemotherapy cycles found that intermittent G-CSF administration effectively maintained dose intensity during ABVD treatment for Hodgkin lymphoma, with a very low incidence of febrile neutropenia (0.45%) and no treatment delays.

Intermittent G-CSF, given on specific days, may offer a cost-effective alternative to daily or pegylated G-CSF, while also reducing the risk of side effects like bone pain and potential lung toxicity associated with bleomycin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent granulocyte colony-stimulating factor maintains dose intensity after ABVD therapy complicated by neutropenia. Ho, P., Sherman, P., Grigg, A.[2013]

The G-CSF/G-CSFR signaling pathway significantly enhances the proliferation and survival of bladder cancer cells, as demonstrated by increased cell growth in TCC-SUP cells expressing G-CSFR and larger tumor formation in xenograft models.

Blocking G-CSF with antibodies led to increased apoptosis in bladder cancer cells, indicating that targeting this signaling pathway could be a potential therapeutic strategy for treating invasive bladder carcinomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factor/granulocyte colony-stimulating factor receptor biological axis promotes survival and growth of bladder cancer cells. Chakraborty, A., Guha, S.[2007]

In a study of 70 gastric cancer tissue samples, higher levels of G-CSF were linked to advanced tumor stages and shorter overall survival, suggesting that G-CSF could serve as a potential tumor marker for identifying patients who may benefit from anti-angiogenic therapies.

G-CSF promotes tumor growth and angiogenesis through the JAK2/STAT3 signaling pathway, indicating that targeting G-CSF and its receptor could be a promising strategy for improving treatment outcomes in gastric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor Survival. Fan, Z., Li, Y., Zhao, Q., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Comparative Safety Profile Assessment of Oncolytic Virus Therapy Based on Clinical Trials. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Clinical landscape of oncolytic virus research in 2020. [2021]

6. England pubmed.ncbi.nlm.nih.gov

G-CSF receptor expression in ovarian cancer. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

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]

8. England pubmed.ncbi.nlm.nih.gov

Intermittent granulocyte colony-stimulating factor maintains dose intensity after ABVD therapy complicated by neutropenia. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factor/granulocyte colony-stimulating factor receptor biological axis promotes survival and growth of bladder cancer cells. [2007]

10. United States pubmed.ncbi.nlm.nih.gov

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]