ORB-011 for Advanced Cancer

(ORB Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ORB-011, to determine its safety and tolerability in people with advanced solid tumors, such as certain types of breast, lung, or pancreatic cancers. The researchers aim to identify the optimal dose of ORB-011 for treating these cancers. Suitable candidates for this trial have exhausted all standard treatments without success and have cancers like colorectal or triple-negative breast cancer that have recurred or are persistent. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that ORB-011 is likely to be safe for humans?

Research has shown that ORB-011 is being studied to understand its safety in people with advanced solid tumors. This study is in an early stage, meaning researchers are just beginning to assess how well people can handle the treatment.

In these early studies, the main goal is to determine if the drug causes any serious side effects. Researchers first administer the drug in small doses, gradually increasing them to find the highest dose that people can tolerate without major problems.

Since this is an early study, detailed safety information isn't available yet. However, its presence in this initial phase suggests that ORB-011 has shown promise in lab tests or animal studies, warranting testing in humans. This process ensures the treatment might be safe before larger studies are conducted. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced cancer, which often include chemotherapy, radiation, and targeted therapies, ORB-011 introduces a novel approach through dose escalation. Researchers are excited about ORB-011 because it explores a new mechanism of action, potentially targeting cancer cells in a way that existing treatments do not. By escalating dosages in a controlled manner, ORB-011 aims to identify the most effective dose with minimal side effects, offering a tailored approach to treatment. This method could lead to more personalized and efficient cancer care, making it a promising option in the fight against advanced cancer.

What evidence suggests that ORB-011 might be an effective treatment for advanced cancer?

Research shows that ORB-011 is designed to help treat advanced solid tumors. This trial tests the new drug's safety and effectiveness for people with hard-to-treat cancers. ORB-011 is a type of immunotherapy, helping the body's immune system fight cancer cells. Although limited data from human studies exist, its mechanism suggests potential in shrinking tumors. Early results from similar treatments have demonstrated that boosting the immune system can lead to smaller tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Robert Petit, PhD

Principal Investigator

SVP Early Clinical Development

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05947474

NCT05947474 | ORB-011 In Patients With Advanced Solid ... The goal of this clinical research study is to determine if an investigational new drug, named ORB-011, developed by Orionis Biosciences is safe and can be ...

2. orionisbio.com orionisbio.com/2023/11/orionis-biosciences-announces-first-patient-dosed-in-phase-1-clinical-trial-of-orb-011-in-patients-with-advanced-solid-tumors/

Orionis Biosciences Announces First Patient Dosed in ... Orionis is evaluating ORB-011 in a Phase 1 open-label dose-escalation study (NCT05947474) for patients with recurrent or refractory solid tumors ...

3. 1stoncology.com 1stoncology.com/blog/orionis-biosciences-announces-first-patient-dosed-in-phase-1-clinical-trial-of-orb-011-in-patients-with-advanced-solid-tumors1234637706/

Orionis Biosciences Announces First Patient Dosed in ... Orionis is evaluating ORB-011 in a Phase 1 open-label dose-escalation study (NCT05947474) for patients with recurrent or refractory solid tumors ...

4. synapse.patsnap.com synapse.patsnap.com/drug/e67f7dfe5fa34ff9b504ee3075a04246

ORB-011 - Drug Targets, Indications, Patents The Phase 1 clinical trial will provide initial safety, pharmacokinetic and pharmacodynamic readouts, and identify a dose of ORB-011 for use in future studies.

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/orionis-solid-tumour-trial/

Orionis doses first subject in solid tumour immunotherapy trial Orionis Biosciences has dosed the first subject in a Phase I clinical trial of immunotherapy ORB-011 to treat advanced solid tumours.