CTX-8371 for Advanced Cancer

Recruiting at 5 trial locations

Overseen By Natalie Warholic

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Compass Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Organ transplant, Active hepatitis, others

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

Compensation: Varies

Number of Visits: 4

73 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CTX-8371, an experimental therapy targeting PD-1 and PD-L1 proteins, for individuals with advanced or metastatic cancers. These cancers have spread and do not respond to standard treatments. The trial aims to determine the optimal dose and observe the body's reaction to the treatment. Participants will be divided into two groups to either explore different doses or expand on findings from the initial group. Suitable candidates have specific cancer types, such as melanoma or lung cancer, that have not improved with previous PD-1/PD-L1 therapies. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that CTX-8371 is likely to be safe for humans?

Research shows that CTX-8371 is a new cancer treatment with a unique mechanism. It blocks two proteins, PD-1 and PD-L1, enhancing the immune system's ability to attack cancer. However, since CTX-8371 is still in early human testing, detailed safety information remains unavailable.

The current study marks the first human trial of CTX-8371. In this early phase, researchers focus on assessing the treatment's safety and tolerability. While earlier lab and animal studies indicated that CTX-8371 might be effective against cancer, its safety in humans is still under investigation. Participants in these early trials help researchers understand potential side effects and patient responses to the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CTX-8371 is unique because it targets specific cancer cells differently than many existing treatments. Unlike traditional chemotherapy, which affects both cancerous and healthy cells, CTX-8371 is designed to selectively attack cancer cells, potentially reducing side effects and improving outcomes. Researchers are excited about CTX-8371 because it represents a new class of targeted cancer therapies, offering hope for more effective and personalized cancer treatment strategies.

What evidence suggests that CTX-8371 might be an effective treatment for advanced cancer?

Research has shown that CTX-8371, a new type of antibody, might outperform current treatments for advanced cancer. It targets two proteins, PD-1 and PD-L1, which help cancer cells evade the immune system. In lab studies, CTX-8371 demonstrated stronger effects against cancer compared to other similar treatments. This trial will evaluate CTX-8371 in two separate arms: a Dose Escalation Cohort and a Dose Expansion Cohort, based on data from the first cohort. These findings suggest it could benefit patients with hard-to-treat cancers. Early signs are promising, but more studies in humans are needed to confirm its effectiveness. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CTX-8371

Trial Overview

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.

How Is the Trial Designed?

Group I: Dose Expansion Cohort 2 Experimental Treatment 1 Intervention

Two CTX-8371 dose groups (3.0 mg/kg and 10.0 mg/kg) in two tumor type subgroups (NSCLC and TNBC)

Group II: Dose Escalation Cohort 1 Experimental Treatment 1 Intervention

Escalating doses of CTX-8371

Who Is Running the Clinical Trial?

Compass Therapeutics

Lead Sponsor

Trials

5

Recruited

430+

Published Research Related to This Trial

PD-L1 is a critical factor in regulating T-cell activation and immune response, particularly in non-small cell lung cancer (NSCLC), where higher PD-L1 expression is associated with better responses to PD-1 inhibitors like pembrolizumab.

The study emphasizes the importance of assessing PD-L1 expression levels across different lung cancer subtypes, as this can significantly influence treatment decisions and the effectiveness of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies? Ullah, A., Pulliam, S., Karki, NR., et al.[2022]

In a phase II study of 39 patients with advanced non-small cell lung cancer (NS-NSCLC) and high PD-L1 expression, the combination of atezolizumab and bevacizumab resulted in a promising objective response rate of 64.1%, indicating significant efficacy in this patient population.

The treatment showed a 12-month progression-free survival rate of 54.9% and an overall survival rate of 70.6%, with manageable safety profiles, as no patients experienced severe toxicity (grade 4/5), although some did experience serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study). Seto, T., Nosaki, K., Shimokawa, M., et al.[2022]

Insulin and EGF play a crucial role in increasing PD-L1 levels on colon cancer stem cells (CSCs), with insulin activating the PI3K/Akt/mTOR pathway to boost PD-L1 expression, while EGF enhances its transport to the cell surface.

Targeting the insulin and EGF pathways may improve cancer immunotherapy strategies by reducing PD-L1 levels on CSCs, potentially making them more susceptible to immune attacks when combined with PD-1/PD-L1 antibody treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insluin and epithelial growth factor (EGF) promote programmed death ligand 1(PD-L1) production and transport in colon cancer stem cells. Chen, M., Sharma, A., Lin, Y., et al.[2020]

In a systematic review of 125 clinical trials involving over 20,000 patients, 66% experienced at least one treatment-related adverse event from PD-1 and PD-L1 inhibitors, with fatigue, pruritus, and diarrhea being the most common.

Nivolumab was found to have a higher incidence of adverse events compared to pembrolizumab, and PD-1 inhibitors generally led to more severe adverse events than PD-L1 inhibitors, highlighting the importance of understanding these differences for clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis. Wang, Y., Zhou, S., Yang, F., et al.[2022]

In a study of 120 patients with stage I-III non-small cell lung cancer (NSCLC), serum exosomal PD-L1 levels were found to significantly correlate with tumor PD-L1 expression and the presence of CD8+ tumor-infiltrating lymphocytes, indicating their potential role in predicting immunotherapy efficacy.

Patients with higher levels of exosomal PD-L1 (≥166 pg/mL) showed a 100% disease control rate when treated with anti-PD-1 therapy, suggesting that measuring exosomal PD-L1 could be a valuable tool for predicting treatment response and clinical outcomes in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer. Shimada, Y., Matsubayashi, J., Kudo, Y., et al.[2021]

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 review of 23 randomized controlled trials involving 15,797 patients, PD-1 inhibitors significantly improved overall survival (OS) by an average of 4.80 months compared to standard care, while PD-L1 inhibitors improved OS by 2.59 months.

PD-1 inhibitors were found to provide greater OS benefits than PD-L1 inhibitors, suggesting that PD-1 inhibitors may be the preferred choice for treating advanced non-small-cell lung cancer (NSCLC), especially in patients with varying PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Yi, K., Zhu, Q., Kuang, YK., 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 study of 241 solid tumor patients treated with anti-PD-1/PD-L1 antibodies, 77.6% experienced immune-related adverse events (irAEs), with skin toxicities being the most common (46.1%).

Patients who developed any irAE had significantly better progression-free survival (PFS) and overall survival (OS) compared to those without irAEs, suggesting that while some irAEs can be severe, their occurrence may indicate a more favorable treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events and outcomes among pan-cancer patients receiving immune checkpoint inhibitors: A monocentric real-world observational study. Ge, X., Jiang, W., Li, H., et al.[2023]

In a study of 80 lung adenocarcinoma patients, 11.3% exhibited high PD-L1 expression (TPS ≥50%), indicating that a subset of patients with known driver oncogenes may be candidates for PD-1/PD-L1 inhibitors.

Patients with a PD-L1 tumor proportion score (TPS) of ≥1% experienced significantly poorer progression-free survival on initial TKI treatment compared to those with a TPS of <1%, suggesting that PD-L1 expression may impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK rearrangements. Yoneshima, Y., Ijichi, K., Anai, S., et al.[2022]

A study found that dermatitis, specifically lichenoid and spongiotic types, occurred in patients treated with PD-1/PD-L1 inhibitors and was associated with a significantly higher tumor response rate (65% vs. 17% for controls).

Patients with dermatitis showed longer progression-free and overall survival times compared to those without, suggesting that dermatitis may indicate a stronger immune response and better cancer outcomes, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study. Min Lee, CK., Li, S., Tran, DC., et al.[2020]

In a study of 2031 PD-L1 tests from 1795 patients with non-small cell lung cancer (NSCLC), it was found that 41.6% had low PD-L1 expression (TPS < 1%), while 29.8% had high expression (TPS ≥ 50%), indicating significant variability in PD-L1 levels among patients.

The study revealed that small biopsy samples (less than 8 mm²) had a higher discordance rate in PD-L1 status compared to larger samples, suggesting that biopsies from metastatic sites may provide more accurate assessments of PD-L1 expression and potentially improve treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Heterogeneity of PD-L1 Expression by 22C3 Assay in Routine Population-Based and Reflexive Clinical Testing in Lung Cancer. Hwang, DM., Albaqer, T., Santiago, RC., et al.[2021]

In a study of 19 patients with locally advanced non-small cell lung cancer (LA-NSCLC) undergoing concurrent chemoradiotherapy, 68% showed positive PD-L1 expression, but this did not significantly correlate with age, smoking history, or tumor staging.

Patients with PD-L1 expression less than 25% had better overall survival rates compared to those with higher PD-L1 levels, suggesting that lower PD-L1 expression may be associated with a more favorable prognosis in LA-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[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]. Xue, WJ., Bi, N., Yang, L., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10877993/

A bispecific anti-PD-1 and PD-L1 antibody induces ...

CTX-8371 is a novel checkpoint inhibitor that might provide greater clinical benefit compared to current anti-PD-1 and PD-L1 antibodies.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06150664

Study Details | NCT06150664 | A Phase 1 of CTX-8371 in ...

This Phase 1, open-label, first-in-human study will evaluate the safety, tolerability, immunogenicity, and pharmacokinetic profile of CTX-8371 monotherapy.

3.

investors.compasstherapeutics.com

investors.compasstherapeutics.com/news-releases/news-release-details/compass-therapeutics-reports-2025-second-quarter-financial

Compass Therapeutics Reports 2025 Second Quarter ...

In the ongoing Phase 1 dose-escalation study of CTX-8371 (PD-1 x PD-L1 bispecific antibody) in patients treated in the post-checkpoint inhibitor ...

4.

clin.larvol.com

clin.larvol.com/trial-detail/NCT06150664

A Phase 1 of CTX-8371 in Patients With Advanced ...

CTX-8371 provides enhanced anti-tumor activity relative to approved anti-PD-1 and PD-L1 therapies in a series of in vitro and in vivo experimental settings and ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38379869/

A bispecific anti-PD-1 and PD-L1 antibody induces ...

CTX-8371 is a novel checkpoint inhibitor that might provide greater clinical benefit compared to current anti-PD-1 and PD-L1 antibodies.

6.

investors.compasstherapeutics.com

investors.compasstherapeutics.com/news-releases/news-release-details/compass-therapeutics-announces-publication-ctx-8371-preclinical

Compass Therapeutics Announces Publication of CTX ...

The data highlighted the unique mechanism-of-action of CTX-8371, inducing dual blockade of PD-1 and PDL-1 and cleavage of cell surface PD-1. In ...

7.

globenewswire.com

globenewswire.com/news-release/2025/11/05/3181347/0/en/Compass-Therapeutics-Reports-Third-Quarter-2025-Financial-Results-and-Provides-Corporate-Update.html

Compass Therapeutics Reports Third Quarter 2025 Financial

A new response in a third indication has been observed in the fifth and final dosing cohort of the Phase 1 dose-escalation study of CTX-8371 (PD ...