ORB-011 for Advanced Cancer (ORB Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Orionis Biosciences Inc
No Placebo Group
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.
What safety data is available for ORB-011 in advanced cancer treatment?The provided research does not specifically mention ORB-011 or its safety data. However, it discusses the safety profiles of immune checkpoint inhibitors, particularly PD-1/PD-L1 inhibitors, which are relevant to advanced cancer treatment. These studies highlight the occurrence of immune-related adverse events (irAEs) and hepatic toxicities associated with these treatments. The research emphasizes the importance of managing these adverse events to optimize treatment outcomes.4571214
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 participate if you are on other investigational agents, have had anticancer therapy within 28 days, or are using immunosuppressive medication within 28 days before ORB-011 treatment. It's best to discuss your specific medications with the trial team.
Is the drug ORB-011 a promising treatment for advanced cancer?The information provided does not mention ORB-011, so we cannot determine if it is a promising treatment for advanced cancer based on the given research articles.1381115
What data supports the idea that ORB-011 for Advanced Cancer is an effective treatment?The available research does not provide specific data on ORB-011 for Advanced Cancer. However, it discusses the effectiveness of immune checkpoint inhibitors (ICIs), a type of treatment for advanced cancers. For example, in a study from Denmark, patients with advanced non-small cell lung cancer (NSCLC) showed improved overall survival rates after the introduction of ICIs. The 3-year survival rate increased from 6% to 18% after ICIs were implemented. This suggests that treatments like ICIs can be effective for advanced cancers, but specific data on ORB-011 is not available in the provided information.2691013
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.Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Dose Escalation ORB-011Experimental Treatment1 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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Honor Health Research InstituteScottsdale, AZ
MD Anderson CenterHouston, TX
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Who is running the clinical trial?
Orionis Biosciences IncLead Sponsor
References
Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. [2021]This phase I, multicenter, open-label, single-arm, dose-escalation, and dose-expansion study evaluated the safety, tolerability, and antitumor activity of MEDI-573 in adults with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
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]To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) trials.
Pembrolizumab Shows Promise for NSCLC. [2015]Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.
Managing Adverse Events With Immune Checkpoint Agents. [2017]Immune checkpoint inhibitors (anti-cytotoxic T-lymphocyte antigen 4 and anti programmed cell death 1/programmed cell death 1 ligand antibodies) have shown impressive clinical activity in multiple cancer types. Despite achieving great clinical success, challenges and limitations of these drugs as monotherapy or various combinational strategies include the development of a unique set of immune-related adverse events (irAEs) that can be severe and even fatal. Therefore, identification of patients at risk, prevention, consistent communication between patients and medical team, rapid recognition, and treatment of irAEs are critical in optimizing treatment outcomes. This review focuses on the description of more common irAEs and provides a suggested approach for management of specific irAEs.
Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis. [2018]Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors.
Exploration of a Novel Intermediate Response Endpoint in Immunotherapy Clinical Studies. [2019]Purpose: Both objective response rate (ORR) and progression-free survival as defined by RECIST are weakly associated with overall survival (OS) in trials evaluating immunotherapy drug products. We proposed a novel intermediate response endpoint (IME) for evaluating immunotherapies.Experimental Design: We defined IME response as having no nontarget lesion progression, no new lesion appearance, and reaching a target lesion response determined by baseline tumor burden, tumor reduction depth, and tumor change dynamics within one year after randomization. Database used consisted of data from randomized active-controlled immunotherapy trials. Criterion for IME was developed on the basis of patient-level data from a training dataset, and further evaluated using an independent testing dataset. A patient-level responder analysis comparing OS between patients with and without an IME response was conducted using combined data. Association between trial-level OS hazard ratio (HR) and IME odds ratio (OR) was analyzed using a weighted linear regression model.Results: A total of 5,806 patients from 9 randomized studies were included in the database. At patient level, patients with IME response had improved OS compared with nonresponders (HR = 0.09). At trial level, association between OS and IME was moderate (R2 = 0.68).Conclusions: The IME was moderately associated with OS, and the association appeared to be stronger than the association observed between RECIST-defined ORR and OS. However, the analyses conducted in this research are exploratory and further evaluation is needed before using this endpoint in future studies. Clin Cancer Res; 24(10); 2262-7. ©2017 AACR.
Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors. [2022]Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.
Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies. [2020]The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies.
Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. [2023]Immune checkpoint inhibitors (ICIs) are rapidly being incorporated as treatment option either alone or in combination with chemotherapy in most of the solid tumors. Since there is very limited data of ICI in patients with poor performance status (PS) from the real world settings, we performed a retrospective audit of patients who received ICI and report the analysis based on ECOG PS of these patients.This study is a retrospective audit of a prospectively collected database of patients receiving ICIs for advanced solid tumors in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. All statistical calculations were performed using SPSS statistical software for windows version 20.0.A total of 155 patients who received ICIs during the specified period were evaluated for this study. Baseline ECOG PS 0-1 (n = 103, 66.4%) patients was associated with median OS 9.1 (95% CI [confidence interval], 4.4-NR) months when compared to ECOG 2-4 (n = 52, 33.5%) which had a median OS of 2.9 (95% CI; 1.8-5.5) months (HR, 1.7, 95% CI, 1.1-2.7, log rank P = .017). The disease control rate for the poor PS group was 34.6%. However, 27.3% patients (95% CI: 20.3-34.3) were still alive at 1 year. Median OS in patients with PS 2 was 3.7 months (95% CI: 0-11.6) as compared to 1.8 months (95% CI: 0.2-3.4) for those with PS 3-4 (HR-2.0; 95% CI: 1.0-3.9, P = .041). The tolerance to ICIs was good with no grade 3/4 toxicities in 44 (84.6%) patients.Immune checkpoint inhibitors are a safe and effective therapeutic option even in solid tumor patients with poor performance status.
Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC-Real World Efficacy. [2021]Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6-20.0) and 6% (95% CI 5.1-7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis.
Very high PD-L1 expression as a prognostic indicator of overall survival among patients with advanced non-small cell lung cancer receiving anti-PD-(L)1 monotherapies in routine practice. [2023]Programmed death or ligand-1 (PD-(L)1) pathway inhibitors confer improved survival as the first-line treatment for advanced non-small cell lung cancer (aNSCLC) in patients with PD-L1 expression (PD-L1 + e ≥ 50%) compared to platinum-doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients with PD-L1 + e of ≥50% receiving pembrolizumab monotherapy, very high levels of PD-L1 + e (≥90%) may be associated with better outcomes. We sought to assess whether very high PD-L1 + e (≥90%) compared to high PD-L1 + e (50%-89%) is associated with an overall survival benefit in aNSCLC patients receiving anti-PD-(L)1 monotherapies.
Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. [2022]With the increased use of immune checkpoint inhibitors (ICIs) in advanced lung cancer, adverse events (AEs), particularly immune-related AEs (irAEs), have garnered considerable interest. We conducted a comprehensive assessment of the toxicity profile in advanced lung cancer using multi-source medical data.
Overall survival of individuals with metastatic cancer in Sweden: a nationwide study. [2022]Consistent improvements for overall survival (OS) have been reported for individuals with metastatic cancer. Swedish population-based registers allow national coverage and long follow-up time. The aim of this study was to estimate and explore long-term OS of individuals diagnosed with metastatic cancer using Swedish nationwide health registers.
Adverse reactions and efficacy of camrelizumab in patients with lung adenocarcinoma with high PD-L1 expression: A case report. [2023]Immune checkpoint inhibitors have been rapidly developed for lung cancer therapy and major clinical guidelines have recommended them as the optimal first-line treatment for PD-L1-positive advanced lung cancer. Unfortunately, there is a lack of efficient prediction tools for the occurrence of immune-related adverse events (irAEs) caused by immunotherapy, and there is a lack of real-world data on the processing of irAEs, particularly those occurring in multiple systems simultaneously.
Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors. [2023]Report of a Phase 1 dose-escalation study of OBI-3424 monotherapy in patients with advanced solid tumors (NCT03592264).