CTX-8371 for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Compass Therapeutics
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Pregnancy, Organ transplant, Active hepatitis, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a Phase 1, open-label, first-in-human study of CTX-8371 administered as a monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 cohorts: Dose Escalation and Dose Expansion.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had systemic therapy with immunosuppressive agents within 7 days before starting the trial treatment.
What data supports the effectiveness of the drug CTX-8371 for advanced cancer?
The research shows that PD-1 and PD-L1 inhibitors, which are similar to components of CTX-8371, have shown promising results in treating advanced non-small-cell lung cancer (NSCLC). Additionally, PD-L1 expression is a marker of treatment efficacy, suggesting that targeting PD-1/PD-L1 pathways can be effective in cancer treatment.
12345What safety information is available for CTX-8371 (PD-1 x PD-L1) in humans?
Drugs targeting PD-1 and PD-L1, like CTX-8371, can cause side effects such as skin issues (dermatitis) and other immune-related reactions. These side effects have been observed in various cancer treatments using similar drugs.
678910What makes the drug CTX-8371 unique for treating advanced cancer?
CTX-8371 is unique because it targets both PD-1 and PD-L1, which are proteins involved in suppressing the immune system's ability to attack cancer cells. This dual targeting approach may enhance the immune response against cancer compared to treatments that target only one of these proteins.
25111213Eligibility Criteria
This trial is for adults with advanced cancers like breast cancer, lung cancer, or melanoma that have stopped responding to standard treatments. Participants must have tried a PD-1/PD-L1 inhibitor and, if they have a specific mutation (BRAF V600), also BRAF/MEK inhibitors.Inclusion Criteria
My Hodgkin Lymphoma did not fully respond to anti-PD-1 treatment.
I am fully active or can carry out light work.
My blood tests show enough neutrophils, platelets, and hemoglobin.
+24 more
Exclusion Criteria
I haven't taken strong immune system drugs in the last week, except for creams, nasal sprays, eye drops, or inhalers.
I have had an organ transplant.
I stopped PD-1 or PD-L1 therapy due to a severe side effect.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants receive escalating doses of CTX-8371 to evaluate safety and tolerability
6 months
IV infusion every 2 weeks
Dose Expansion
Participants receive CTX-8371 at doses determined from the Dose Escalation phase
up to 2 years
IV infusion every 2 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days
Participant Groups
The study tests CTX-8371 as a solo treatment in two parts: first finding the right dose and then seeing how well it works at that dose. It's for patients whose cancers haven't responded to other therapies.
2Treatment groups
Experimental Treatment
Group I: Dose Expansion Cohort 2Experimental Treatment1 Intervention
Dose of CTX-8371 depending on Cohort 1 data
Group II: Dose Escalation Cohort 1Experimental Treatment1 Intervention
Escalating doses of CTX-8371
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Florida Cancer Specialists - SarasotaSarasota, FL
Florida Cancer Specialists - Lake NonaOrlando, FL
Dana-Farber Cancer InstituteBoston, MA
D&H Cancer Research CenterMargate, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Compass TherapeuticsLead Sponsor
References
Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study). [2022]PD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models.
The relative and absolute benefit of programmed death receptor-1 vs programmed death ligand 1 therapy in advanced non-small-cell lung cancer: A systematic review and meta-analysis. [2021]Programmed death receptor-1 (PD-1) and its ligand (PD-L1) inhibitors have shown promising results in treating advanced non-small-cell lung cancer (NSCLC). Our objective was to compare the relative and absolute benefits between PD-1 and PD-L1 inhibitors in advanced NSCLC.
Insluin and epithelial growth factor (EGF) promote programmed death ligand 1(PD-L1) production and transport in colon cancer stem cells. [2020]Programmed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expressed on cancer cells to mediate cancer escape through interaction with PD-1 expressed on activated T lymphocytes (T cells). Previously, we reported that colon and breast cancer stem cells (CSCs) expressed much higher levels of PD-L1 than their parental cells, suggesting they will be more resistant to immune attack.
[Expression and prognostic value of programmed cell death ligand 1 in patients with locally advanced and non-EGFR-mutated non-small cell lung cancer receiving concurrent chemoradiotherapy]. [2022]Objective: To explore the expression of programmed cell death ligand 1 (PD-L1) in patients with locally advanced and non-EGFR-mutated non-small cell lung cancer (LA-NSCLC) undergoing concurrent chemoradiotherapy (cCRT) and its association with clinical outcome of patients. Methods: The basic clinical information of 19 patients with unresectable, non-EGFR mutated LA-NSCLC receiving radical cCRT in Cancer Hospital Chinese Academy of Medical Sciences from January 2016 to December 2017 was retrospectively analyzed. The rabbit monoclonal antibody SP263 was used for immunohistochemical analysis to detect the expression of PD-L1 in LA-NSCLC tissues and the tumor proportion score (TPS) equal to or greater than 1% was defined as PD-L1 positive. The associations between PD-L1 ≥1% and PD-L1 ≥25% with the clinical characteristics and clinical outcome of LA-NSCLC patients were evaluated respectively. Results: Among 19 LA-NSCLC patients, 13 had PD-L1 positive expression, and 4 had PD-L1 expression greater than or equal to 25%. No significant difference was observed between patients with PD-L1 positive and negative expressions regarding the distribution of age, smoking history, pathological classification, and TNM staging (P>0.05). A total of 15 patients could be evaluated for therapeutic effect, including 7 patients with partial response (PR), 7 patients with stable disease (SD), and 1 patient with progressive disease (PD). In the group with PD-L1 expression<1%, 3 patients were in objective response, and 4 patients were in disease control. In the group with PD-L1 expression ≥1%, 4 patients were in objective response, and 10 patients were in disease control. When the PD-L1 expression was less than 25%, 6 patients gained the objective response, and 11 patients gained the disease control. When the PD-L1 expression was greater than or equal to 25%, 1 patient gained the objective response, and 3 patients gained the disease control. The median overall survival (OS) was 35 (95%CI: 12.7-57.3) months for patients with PD-L1 ≥1% and 40 (95%CI: not reaching the end point) months for patients with PD-L1<1% (P=0.284). Patients with PD-L1 ≥25% had a median survival time of 12 (95%CI:0.0-34.5) months, and patients with PD-L1<25% had a median survival time of 40 (95%CI: 27.4-52.6) months (P=0.241). Conclusions: The prognosis of LA-NSCLC patients with PD-L1 positive and no-EGFR mutation receiving concurrent chemoradiation has a trend of poor prognosis. A larger sample size study is warranted to explore the prognostic value of PD-L1 expression in inoperable LA-NSCLC patients and to further explore the effect of immunotherapy on patients with different PD-L1 expression levels.
Prevalence and Heterogeneity of PD-L1 Expression by 22C3 Assay in Routine Population-Based and Reflexive Clinical Testing in Lung Cancer. [2021]Programmed death-ligand 1 (PD-L1) is used as a biomarker for anti-programmed cell death protein-1 (PD-1) or anti-PD-L1 immunotherapies in NSCLC. We report here the results of population-based PD-L1 testing using the 22C3 IHC pharmDx Assay (Agilent Technologies) in a large Canadian regional reference pathology laboratory.
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]Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) drugs treatment-related adverse events (AEs) are not uniform based on current study for patients with cancer. The study aimed to provide a complete toxicity profile and toxicity spectrum for anti-PD-1 and anti-PD-L1 drugs.
Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study. [2020]Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.
Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis. [2022]Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.
Immune-related adverse events and outcomes among pan-cancer patients receiving immune checkpoint inhibitors: A monocentric real-world observational study. [2023]Real-world evidence on immune-related adverse events (irAEs) are relatively insufficient. Herein patterns and outcomes of irAEs after administration of anti-programmed cell death 1 (PD-1) and its legend 1 (PD-L1) antibodies were investigated.
PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies? [2022]Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation. Activation of T-cells warrants the upregulation of PD-1 and production of cytokines which also upregulate PD-L1 expression, creating a positive feedback mechanism that has an important role in the prevention of tissue destruction and development of autoimmunity. In the context of inadequate immune response, the prolonged antigen stimulation leads to chronic PD-1 upregulation and T-cell exhaustion. In lung cancer patients, PD-L1 expression levels have been of special interest since patients with non-small cell lung cancer (NSCLC) demonstrate higher levels of expression and tend to respond more favorably to the evolving PD-1 and PD-L1 inhibitors. The Food and Drug Administration (FDA) has approved the PD-1 inhibitor, pembrolizumab, alone as front-line single-agent therapy instead of chemotherapy in patients with NSCLC and PD-L1 ≥1% expression and chemoimmunotherapy regimens are available for lower stage disease. The National Comprehensive Cancer Network (NCCN) guidelines also delineate treatment by low and high expression of PD-L1 in NSCLC. Thus, studying PD-L1 overexpression levels in the different histological subtypes of lung cancer can affect our approach to treating these patients. There is an evolving role of immunotherapy in the other sub-types of lung cancer, especially small cell lung cancer (SCLC). In addition, within the NSCLC category, squamous cell carcinomas and non-G12C KRAS mutant NSCLC have no specific targetable therapies to date. Therefore, assessment of the PD-L1 expression level among these subtypes of lung cancer is required, since lung cancer is one of the few malignances wherein PD-L1 expression levels is so crucial in determining the role of immunotherapy. In this study, we compared PD-L1 expression in lung cancer according to the histological subtype of the tumor.
Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer. [2021]PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome's surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I-III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p
PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK rearrangements. [2022]Expression of programmed cell death-ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death-1 (PD-1) pathway blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however.