CT3001 for Advanced Solid Tumors

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Crossignal Therapeutics, Inc.

Must not be taking: Anticancer treatments, Immune suppressants

Disqualifiers: Pregnancy, Severe diseases, QT prolongation, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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. Phase 1 will be a standard 3+3 dose escalation and dose finding study in patients with advanced solid tumors for whom there is no available therapy (or patients are not candidates for such therapy) for the assessment of DLTs at up to 6 dose levels of CT3001. Phase 2a is a dose expansion study to evaluate the preliminary efficacy of CT3001 in patients with advanced CRC or PDAC.

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.

What data supports the idea that CT3001 for Advanced Solid Tumors is an effective treatment?

The available research shows that drugs targeting PD-1 and PD-L1, like CT3001, have shown promise in treating advanced solid tumors. Studies indicate that 10-40% of patients with advanced cancer experience improved survival when treated with these inhibitors. Additionally, these drugs have been effective in various types of cancer, including lung, kidney, and ovarian cancers, suggesting that CT3001 could be a beneficial option for patients with advanced solid tumors. ^{1 2 3 4 5}

What safety data exists for CT3001 treatment?

The provided research does not specifically mention CT3001, CT-3001, or CT 3001. However, it discusses the safety profiles of PD-1/PD-L1 inhibitors, which are related to immune checkpoint therapies. These studies highlight the importance of understanding toxicities and managing adverse events associated with PD-1/PD-L1 blockade, which may be relevant if CT3001 is a similar type of treatment. The research includes systematic reviews and real-world studies on adverse events, particularly in treatments for advanced melanoma and non-small cell lung cancer, indicating that PD-1 inhibitors generally have lower risks of high-grade adverse events compared to other treatments. ^{6 7 8 9 10}

Is the treatment CT3001 a promising treatment for advanced solid tumors?

CT3001, a type of CAR T-cell therapy, shows promise in treating advanced solid tumors. Early trials have reported encouraging response rates in various cancers, such as ovarian, gastric, and colorectal cancers. This treatment uses the body's own immune cells to target and attack cancer cells, and it has been well-tolerated in patients so far. ^{11 12 13 14 15}

Research Team

Zhi (Zak) Liang Chu, Ph.D.

Principal Investigator

Crossignal Therapeutics

Eligibility Criteria

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 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• CT3001 (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. United States 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. [2022]

3. England 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. [2021]

4. New Zealand 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. [2022]

5. Switzerland 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

7. United States 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. [2022]

9. Switzerland 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. [2020]

10. Switzerland 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. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Adoptive T-Cell Therapy for Solid Tumors. [2023]

12. United States 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. [2021]

13. Iran pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells immunotherapy for targeting breast cancer. [2021]

14. United States 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. [2021]

15. New Zealand pubmed.ncbi.nlm.nih.gov

Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors. [2021]