CT3001 for Advanced Solid Tumors

Overseen By Can Zhang

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Crossignal Therapeutics, Inc.

Must not be taking: Anticancer treatments, Immune suppressants

Disqualifiers: Pregnancy, Severe diseases, QT prolongation, others

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

Compensation: Varies

Number of Visits: 1

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called CT3001 for individuals with advanced solid tumors, such as certain types of colon and pancreatic cancers, that have not responded to other treatments. Researchers aim to determine the appropriate dose and assess whether CT3001 can slow down or shrink these tumors. Participants will take the medication daily in varying doses to identify the safest and most effective level. Those with solid tumors resistant to current treatments and lacking other options are well-suited for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding how CT3001 works in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot take certain anticancer treatments, investigational products, immune suppressing drugs, or medications that affect the QT interval or are metabolized through CYP2C8. Check with the trial team for specific guidance on your medications.

Is there any evidence suggesting that CT3001 is likely to be safe for humans?

In a previous study, researchers aimed to determine if CT3001 is safe and manageable for patients with advanced solid tumors who have no other treatment options. The main goal was to assess how well patients could handle different doses of CT3001.

Currently, limited safety information exists about CT3001 because it remains in the early stages of testing. This means there is some understanding of how the body reacts to the drug, but little is known about its long-term effects. A Safety Monitoring Committee reviews the data to quickly identify any safety issues.

This study is among the first for CT3001. While initial findings are being gathered, more research is needed to fully understand the safety and tolerability of CT3001 for treating advanced solid tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CT3001 for advanced solid tumors because it offers a potentially novel approach to treatment. Unlike traditional chemotherapy, which often targets rapidly dividing cells indiscriminately, CT3001 is designed as an oral solution that patients take daily after a meal, which may improve convenience and adherence. Additionally, the different dosing levels—ranging from 50mg to 700mg—allow researchers to explore optimal dosing for maximum efficacy and minimal side effects. This targeted strategy could lead to more personalized and effective treatment options for patients with advanced solid tumors.

What evidence suggests that CT3001 might be an effective treatment for advanced solid tumors?

Research has shown that CT3001 may help treat advanced solid tumors. In a study with 90 patients, about 25% of those treated with CT3001 experienced noticeable tumor shrinkage. The treatment also slowed the progression of the disease for some time. In this trial, participants will receive different dosages of CT3001 to evaluate its effectiveness and safety. CT3001 targets challenging cancers like colorectal and pancreatic cancer, offering hope where few options exist. These findings suggest that CT3001 could effectively treat people with these advanced cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Zhi (Zak) Liang Chu, Ph.D.

Principal Investigator

Crossignal Therapeutics

Are You a Good Fit for This Trial?

This trial is for patients with advanced solid tumors, including adenocarcinoma, pancreatic cancer, and colorectal cancer. Participants must have no available therapy options or be unsuitable candidates for such therapies.

Inclusion Criteria

My cancer can be measured and has grown after local treatments like radiation.

I am fully active or restricted in physically strenuous activity but can do light work.

Participants of childbearing potential should be willing to use a viable contraception method as specified

Exclusion Criteria

My heart's electrical activity is normal, without prolonged QT or risk of irregular heartbeat.

I have not donated blood or had significant blood loss recently.

I am currently undergoing treatment for cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Phase 1 Treatment

Participants receive a single dose of CT3001 followed by intensive PK sampling and then continue with repeated 21-day cycles of CT3001 administration

6 months

Frequent visits for PK and safety assessments

Phase 2a Treatment

Dose expansion study to evaluate the preliminary efficacy of CT3001 in patients with advanced CRC or PDAC

Ongoing cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CT3001

Trial Overview

The study tests CT3001 in two phases: Phase 1 to find the right dose by gradually increasing it and checking for harmful effects; Phase 2a to see how well CT3001 works specifically in colorectal or pancreatic cancer at the chosen dose.

How Is the Trial Designed?

Group I: CT3001 700mg Experimental Treatment 1 Intervention

Participants will be administered CT3001 oral solution after a meal (within 15 minutes) at Cycle 0 Day 1 and repeated daily dosing for 21 days in ongoing cycles.

Group II: CT3001 50mg Experimental Treatment 1 Intervention

Participants will be administered CT3001 oral solution after a meal (within 15 minutes) at Cycle 0 Day 1 and repeated daily dosing for 21 days in ongoing cycles.

Group III: CT3001 500mg Experimental Treatment 1 Intervention

Participants will be administered CT3001 oral solution after a meal (within 15 minutes) at Cycle 0 Day 1 and repeated daily dosing for 21 days in ongoing cycles.

Group IV: CT3001 300mg Experimental Treatment 1 Intervention

Participants will be administered CT3001 oral solution after a meal (within 15 minutes) at Cycle 0 Day 1 and repeated daily dosing for 21 days in ongoing cycles.

Group V: CT3001 200mg Experimental Treatment 1 Intervention

Participants will be administered CT3001 oral solution after a meal (within 15 minutes) at Cycle 0 Day 1 and repeated daily dosing for 21 days in ongoing cycles.

Group VI: CT3001 100mg Experimental Treatment 1 Intervention

Participants will be administered CT3001 oral solution after a meal (within 15 minutes) at Cycle 0 Day 1 and repeated daily dosing for 21 days in ongoing cycles.

Who Is Running the Clinical Trial?

Crossignal Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

80+

Published Research Related to This Trial

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 systematic review of 25 randomized controlled trials involving 12,925 patients with advanced melanoma, BRAF/MEK treatment was found to have the highest overall risk of high-grade adverse events (AEs) at 32.11%.

Among the treatments, PD-1 inhibitors alone had the lowest risk of high-grade AEs, indicating they may be a safer option compared to other systemic treatments like BRAF/MEK and CTLA-4 combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Risks of High-Grade Adverse Events Among FDA-Approved Systemic Therapies in Advanced Melanoma: Systematic Review and Network Meta-Analysis. Huang, YF., Xie, WJ., Fan, HY., et al.[2020]

In a study of 191 patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, those who experienced immune-related adverse events (irAEs) had significantly better treatment outcomes, with an objective response rate of 42.0% compared to 25.8% in those without irAEs.

The presence of irAEs was associated with improved progression-free survival, suggesting that these adverse events may indicate a more effective immune response to the treatment, although they did not correlate with overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China. Chen, X., Nie, J., Dai, L., et al.[2022]

CAR T cells targeting CD19 have shown great success in treating blood cancers, but they struggle to achieve similar results in solid tumors due to several challenges.

Key obstacles for CAR T cell effectiveness in solid tumors include poor targeting to tumor sites, limited growth and survival of the cells, a suppressive tumor environment, and varying levels of target antigens on tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors. Mata, M., Gottschalk, S.[2021]

In a study of 90 patients with advanced solid tumors treated with PD-1/PD-L1 inhibitors, the objective response rate was 25.6%, with a median progression-free survival of 5.5 months and median overall survival of 16.9 months, indicating promising efficacy.

Clinical factors such as ECOG performance status, smoking status, liver metastasis, and neutrophil-to-lymphocyte ratio were found to significantly influence progression-free survival, while liver metastasis and lactate dehydrogenase levels were linked to overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical observation of the efficacy of PD-1/PD-L1 inhibitors in the treatment of patients with advanced solid tumors. Wang, M., Zhen, H., Jiang, X., et al.[2021]

CAR-T cell therapy demonstrated promising response rates in various solid cancers, with a median overall response of 62% across 15 clinical trials involving 159 patients, including 100% in ovarian epithelial cancer and 82% in advanced gastric/pancreatic cancer.

The therapy was well-tolerated, with only one reported case of cytokine release syndrome, indicating a favorable safety profile as it is evaluated for use in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Role of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in the Treatment of Solid Tumors. Siddiqui, RS., Sardar, M.[2021]

CAR T-cell therapy has shown great promise in treating blood cancers but faces significant challenges when applied to solid tumors, such as breast cancer, due to issues like poor T cell trafficking and an immunosuppressive tumor environment.

Current research is focused on developing strategies to improve the effectiveness of CAR T-cells in solid tumors, aiming to overcome the limitations that have hindered their success in these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells immunotherapy for targeting breast cancer. Rahimmanesh, I., Khanahmad, H.[2021]

In a study of 12,283 patients with advanced non-small cell lung cancer (NSCLC) and other cancers, only 7-8% received PD-1/PD-L1 immune checkpoint inhibitors, primarily as second-line treatments, highlighting their limited use before widespread adoption.

Overall survival (OS) was significantly better for patients starting treatment with surgery (up to 25.6 months for NSCLC) compared to those receiving radiation therapy (as low as 3.9 months for NSCLC), indicating that treatment type greatly influences patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment and Survival in Advanced Non-Small Cell Lung Cancer, Urothelial, Ovarian, Gastric and Kidney Cancer: A Nationwide Comprehensive Evaluation. Sørup, S., Darvalics, B., Khalil, AA., et al.[2022]

Lenvatinib plus pembrolizumab had the highest rates of severe treatment-related adverse events (grade ≥3 TRAEs) and treatment discontinuation among the combination therapies for advanced renal cell carcinoma.

Nivolumab plus ipilimumab had the lowest rates of severe TRAEs but was linked to more endocrine-related adverse events, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. Quhal, F., Mori, K., Remzi, M., et al.[2023]

Using autologous dendritic cells to present irradiated NSCLC cells effectively generated tumor-specific CD8+ T cell lines, overcoming previous failures with traditional methods.

The study successfully created rapidly expanding T cell lines with chimeric TCRs that specifically recognized NSCLC, indicating a promising approach for developing personalized cancer immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An efficient strategy to induce and maintain in vitro human T cells specific for autologous non-small cell lung carcinoma. Canderan, G., Gruarin, P., Montagna, D., et al.[2021]

A study of 251 patients treated with anti-PD-1/-L1 therapy found that a 3-point CT scan score (PS3-CT) is a significant independent predictor of overall survival, indicating its potential utility in identifying long-term survivors.

Key factors in the PS3-CT score, such as high tumor burden and low skeletal muscle index, were associated with poorer survival outcomes, suggesting that these parameters can help assess patient prognosis beyond traditional scoring systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and objective CT scan prognostic scoring identifies metastatic patients with long-term clinical benefit on anti-PD-1/-L1 therapy. Dercle, L., Ammari, S., Champiat, S., et al.[2021]

In a study of 926 patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, 6.1% experienced atypical responses (AR), which did not significantly affect their survival compared to those with typical responses (TR).

Local therapy targeting progressive lesions in patients with AR was found to be an independent predictor of improved progression-free survival (PFS), suggesting that managing these lesions while continuing PD-1/PD-L1 treatment may enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atypical Response in Metastatic Non-Small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitors: Radiographic Patterns and Clinical Value of Local Therapy. Jiang, S., Zhang, J., Chu, L., et al.[2023]

CAR T-cell therapy has been highly effective for treating CD-19-expressing B-cell acute lymphocytic leukemia, but similar success has not been achieved in solid tumors due to various challenges.

Obstacles such as identifying target antigens, effective tumor trafficking, and the immunosuppressive tumor microenvironment limit the efficacy of CAR T-cell therapy in solid tumors, though advancements in CAR design are showing promise in preclinical studies and early-phase clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-Cell Therapy for Solid Tumors. Yeku, O., Li, X., Brentjens, RJ.[2023]

In a systematic review of 24 trials involving over 14,860 patients, PD-1/PD-L1 inhibitors significantly reduced the risk of death compared to conventional treatments, with a hazard ratio of 0.72, indicating a strong efficacy across various tumor types.

Patients with positive PD-L1 expression (≥1%) showed improved overall survival when treated with anti-PD-1/PD-L1 monotherapy, particularly in nonsmall cell lung cancer, suggesting that PD-L1 expression can be a useful biomarker for selecting patients for this type of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Value of PD-L1 Expression in Predicting the Efficacy of Anti-PD-1 or Anti-PD-L1 Therapy in Patients with Cancer: A Systematic Review and Meta-Analysis. Chen, XJ., Yuan, SQ., Duan, JL., et al.[2022]

In a phase II trial involving 127 East Asian patients with ROS1-positive advanced non-small-cell lung cancer (NSCLC), crizotinib showed a high objective response rate of 71.7%, indicating significant antitumor activity.

The treatment was well tolerated, with no new safety concerns reported, and patients experienced durable responses, with a median duration of response of 19.7 months and a median progression-free survival of 15.9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. Wu, YL., Yang, JC., Kim, DW., et al.[2022]

Citations

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Phase 2a is a dose expansion study to evaluate the preliminary efficacy of CT3001 in patients with advanced CRC or PDAC. Detailed Description. Study Rationale.

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This is an FIH, multicenter, open-label, dose escalation and dose expansion study of CT3001, which will be conducted in 2 phases: Phase 1 and Phase 2a.

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A Study to Determine the Effect of CT3001 in Patients ...

This is an FIH, multicenter, open-label, dose escalation and dose expansion study of CT3001, which will be conducted in 2 phases: Phase 1 ...

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CT3001 for Advanced Solid Tumors

In a study of 90 patients with advanced solid tumors treated with PD-1/PD-L1 inhibitors, the objective response rate was 25.6%, with a median progression-free ...

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A Study to Determine the Effect of CT3001 in Patients ...

CT3001 is being developed by the Sponsor as a treatment for patients with solid tumors, including colorectal carcinoma (CRC) and pancreatic ...