ORB-011 for Advanced Cancer

(ORB 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: Pregnancy, Active infections, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called ORB-011 to see if it is safe for people with advanced solid tumors. The study will also find the best dose of the drug by checking its safety and effectiveness.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational agents or have had certain anticancer therapies within 28 days before the study treatment.

What data supports the effectiveness of the drug ORB-011 for advanced cancer?

The research on immune checkpoint inhibitors (ICIs), which are similar to ORB-011, shows that they can be effective in treating advanced solid tumors, even in patients with poor health status. Studies have shown improved overall survival rates in patients with advanced non-small-cell lung cancer after the implementation of ICIs, suggesting potential benefits for similar treatments like ORB-011. ^{1 2 3 4 5}

Research Team

Robert Petit, PhD

Principal Investigator

SVP Early Clinical Development

Eligibility Criteria

Adults with advanced solid tumors who have tried or are ineligible for standard treatments can join this trial. They must be in good physical condition (ECOG 0-1), have proper organ and marrow function, and not be pregnant. Participants should agree to use effective contraception during the study.

Inclusion Criteria

- Serum bilirubin less than or equal to 1.5 × institutional upper limit of normal (ULN)

I am fully active or can carry out light work.

I am a woman who can have children and have a recent negative pregnancy test.

Exclusion Criteria

I can join even if I have a UTI, as long as it's not severe.

Patients who are receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ORB-011 or its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ORB-011 with dose escalation to determine the biologically optimal dose

12 months

End of Treatment

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

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ORB-011

Trial Overview The trial is testing ORB-011, a new drug by Orionis Biosciences, for safety and optimal dosing in treating various advanced solid tumors. The study includes screening, treatment phases, and follows up at the end of treatment.

Participant Groups

Group I: Dose Escalation ORB-011 Experimental Treatment 1 Intervention

ORB-011 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 7 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

In a review of 14 trials involving 12,567 patients with advanced non-small-cell lung cancer (NSCLC), a strong association was found between overall response rate (ORR) and progression-free survival (PFS), indicating that treatments that improve ORR likely also enhance PFS.

However, no significant association was observed between ORR and overall survival (OS), suggesting that while responders have better PFS and OS, factors like treatment cross-over and prolonged survival after disease progression may complicate the relationship between these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. Blumenthal, GM., Karuri, SW., Zhang, H., et al.[2022]

In a study of 155 patients with advanced solid tumors, those with a better performance status (ECOG PS 0-1) had a median overall survival (OS) of 9.1 months, compared to only 2.9 months for those with poorer performance status (ECOG PS 2-4), indicating that performance status significantly impacts treatment outcomes with immune checkpoint inhibitors (ICIs).

Despite having a poor performance status, 27.3% of patients in the study were still alive after one year, and the treatment was generally well-tolerated, with 84.6% of patients experiencing no severe toxicities, suggesting that ICIs can be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. Kapoor, A., Noronha, V., Patil, VM., et al.[2023]

The novel intermediate response endpoint (IME) proposed for evaluating immunotherapies showed a strong association with overall survival (OS), indicating that patients with an IME response had significantly better survival outcomes compared to those without (HR = 0.09).

This study analyzed data from 5,806 patients across 9 randomized trials, finding that the IME was more strongly correlated with OS than traditional RECIST-defined objective response rates, suggesting it could be a more effective measure for assessing immunotherapy efficacy, although further validation is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploration of a Novel Intermediate Response Endpoint in Immunotherapy Clinical Studies. Gao, X., Zhang, L., Sridhara, R.[2019]

Overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) significantly improved after the implementation of immune checkpoint inhibitors (ICIs), with 3-year OS rates rising from 6% pre-approval to 18% post-approval based on a study of 2055 patients.

Prognostic factors for poorer OS in ICI-treated patients included having bone or liver metastases and a performance status of 1 or higher, indicating that these factors should be considered when selecting patients for ICI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC-Real World Efficacy. Mouritzen, MT., Carus, A., Ladekarl, M., et al.[2021]

A study of approximately 69,000 individuals with metastatic cancers in Sweden found that long-term overall survival (OS) varies by cancer type, with the longest median OS observed in metastatic ovarian cancer (MOC) and metastatic breast cancer (MBC).

Survival rates improved for patients diagnosed in 2015 and 2018 compared to earlier years, indicating advancements in treatment or early detection, with estimated cure fractions of 4% for MBC and 1.5% for non-small cell lung cancer (MNSCLC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival of individuals with metastatic cancer in Sweden: a nationwide study. Bütepage, G., Carlqvist, P., Jacob, J., et al.[2022]

References

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

Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. [2022]

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

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. [2023]

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

Exploration of a Novel Intermediate Response Endpoint in Immunotherapy Clinical Studies. [2019]

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

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC-Real World Efficacy. [2021]

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

Overall survival of individuals with metastatic cancer in Sweden: a nationwide study. [2022]