ORB-021 for Cancer

(OR2-01 Trial)

Recruiting at 1 trial location

Overseen By Azza Gadir, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Orionis Biosciences Inc

Must not be taking: Immunosuppressants, Anticancer therapies

Disqualifiers: Uncontrolled illness, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on other investigational drugs or certain anticancer therapies within 28 days before the study. It's best to discuss your specific medications with the trial team.

What is the safety data for ORB-021 in humans?

The safety of drugs similar to ORB-021, which target the PD-1/PD-L1 pathway, has been studied in various cancers. These treatments can cause side effects that are different from traditional chemotherapy, and understanding these is important for safe use. ^{1 2 3 4 5}

How does the drug ORB-021 differ from other cancer treatments?

ORB-021 may be unique in targeting the PD-L1 pathway, which is involved in immune evasion by cancer cells. This approach is different from conventional chemotherapy, as it aims to enhance the body's immune response against cancer cells, potentially offering a new option for cancers that are resistant to standard treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this clinical research study is to determine if an investigational new drug, named ORB-021, developed by Orionis Biosciences is safe and can be tolerated in people diagnosed with an advanced solid tumor. The study also aims to find the biologically optimal dose of the study medicine by assessing the safety and potential activity in the treatment of solid tumors. There are three phases to this study: screening, treatment and end of treatment.

Research Team

Robert Petit, PhD

Principal Investigator

Orionis Biosciences

Eligibility Criteria

This trial is for individuals with advanced solid tumors. Participants must meet certain health criteria, but the specific inclusion and exclusion details are not provided here.

Inclusion Criteria

I have tried or cannot try all standard treatments for my condition.

I am fully active or can carry out light work.

My solid tumor has come back or hasn't responded to treatment, and I can safely have more biopsies.

Exclusion Criteria

I do not have active TB, Hepatitis B or C, HIV, or COVID-19.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ORB-021 or its excipients

Patients who are receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ORB-021 through intravenous infusion/injection with dose escalation based on cohort assignment

12 months

End of Treatment

Participants complete the treatment phase and are assessed for dose-limiting toxicities and adverse events

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ORB-021

Trial Overview The study tests ORB-021, a new drug by Orionis Biosciences, to see if it's safe for people with advanced solid tumors and to find the best dose. The trial includes screening, treatment, and end of treatment phases.

Participant Groups

Group I: Experimental: Dose Escalation ORB-021 Experimental Treatment 1 Intervention

ORB-012 Dose Escalation Participants will be administered study drug at dose levels corresponding to their Cohort. Cohort 1 will be treated with the lowest dose, and the dose will be escalated for future cohorts once the previous dose has been observed not to be associated with DLTs. Up to 5 dose cohorts have been pre-specified. Doses from the escalation arms will be selected as RP2D candidates.

Who Is Running the Clinical Trial?

Orionis Biosciences Inc

Lead Sponsor

Trials

2

Recruited

70+

Findings from Research

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

In a study involving 1738 patients with advanced solid tumors treated with avelumab, a PD-L1 antibody, only 10.2% experienced grade ≥3 treatment-related adverse events (TRAEs), indicating a generally well-tolerated safety profile.

Infusion-related reactions (IRRs) were common, occurring in 25.3% of patients, primarily at the first infusion, but serious IRRs (grade ≥3) were rare, suggesting that while some patients may experience reactions, they are typically manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Kelly, K., Infante, JR., Taylor, MH., et al.[2020]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

This study aims to create a comprehensive toxicity profile for anti-PD-1 and anti-PD-L1 drugs by analyzing systematic reviews and meta-analyses, focusing on treatment-related adverse events in cancer patients.

The research will utilize a network meta-analysis approach to synthesize data from various studies, ensuring a thorough understanding of the safety and adverse effects associated with these immunotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 and anti-PD-L1 drugs treatment-related adverse events for patients with cancer: Protocol for an overview of systematic reviews with meta-analyses. Li, J., Liu, M., Wang, J., et al.[2023]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a study of 56 clear cell carcinoma samples (28 ovarian and 28 endometrial), PD-L1 expression was found to be significantly higher in endometrial clear cell carcinoma (ECCC) compared to ovarian clear cell carcinoma (OCCC), suggesting a potential target for immunotherapy in ECCC.

Mismatch Repair Deficiency (MMR-D) was present in a small number of cases, and while some MMR-D tumors showed PD-L1 expression, there was no significant correlation between PD-L1 levels and cancer stage or patient survival, indicating that PD-L1 expression may not be a reliable prognostic marker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunohistochemical expression of PD-L1 and its correlation with microsatellite status in endometrial and ovarian clear cell carcinomas: a cross-sectional study. Ghasemi, D., Ameli, F., Nili, F., et al.[2023]

In a study of 132 women with epithelial ovarian cancer (EOC), high expression of PD-L1 was found in about 70% of cases, with no significant difference between type I and type II tumors.

High PD-L1 expression in type I EOC was linked to more advanced disease stages, increased recurrence rates, and shorter progression-free survival, suggesting that PD-L1 could be a potential target for therapy in this subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand 1 (PD-L1) Expression in Epithelial Ovarian Cancer: A Comparison of Type I and Type II Tumors Nhokaew, W., Kleebkaow, P., Chaisuriya, N., et al.[2020]

Ovarian clear cell carcinoma (OCCC) is more common in Asian countries and is resistant to standard platinum-based chemotherapy, highlighting the need for alternative treatment strategies.

Targeting the SWI/SNF chromatin remodeling gene mutations, particularly ARID1A, may lead to effective therapies for OCCC, including gemcitabine-based regimens, synthetic lethal approaches, and immune checkpoint blockade, suggesting ARID1A deficiency could serve as a biomarker for personalized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma. Takahashi, K., Takenaka, M., Okamoto, A., et al.[2023]

In a study of 124 patients with advanced-stage ovarian clear cell carcinoma (OCCC), researchers identified that 91% of tumors had alterations in key signaling pathways, particularly the PI3K/AKT/mTOR pathway, indicating a potential target for treatment.

The study found that OCCC cell lines and patient-derived xenografts were highly sensitive to mTORC1/2 inhibition using the drug AZD8055, suggesting it could be an effective treatment strategy for this type of cancer, which is typically resistant to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma. Caumanns, JJ., Berns, K., Wisman, GBA., et al.[2022]

A heavily pretreated patient with recurrent ovarian cancer showed a remarkable complete response to the anti-PD1 immune checkpoint inhibitor pembrolizumab, despite being resistant to standard treatments.

Genomic analysis revealed a unique structural variant in the PD-L1 gene that led to abnormal PD-L1 expression, suggesting that targeting this pathway could be a promising therapeutic strategy for similar cases of chemotherapy-resistant ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Bellone, S., Buza, N., Choi, J., et al.[2022]

References

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

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

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

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]

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

Anti-PD-1 and anti-PD-L1 drugs treatment-related adverse events for patients with cancer: Protocol for an overview of systematic reviews with meta-analyses. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]

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

Immunohistochemical expression of PD-L1 and its correlation with microsatellite status in endometrial and ovarian clear cell carcinomas: a cross-sectional study. [2023]

7. Thailand pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand 1 (PD-L1) Expression in Epithelial Ovarian Cancer: A Comparison of Type I and Type II Tumors [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma. [2023]

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

Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma. [2022]

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

Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. [2022]