UCT-03-008 for Advanced Solid Cancers

Recruiting at1 trial location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: 1200 Pharma, LLC

Disqualifiers: Brain metastases, Cardiac disease, Retinopathy, MDS, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called UCT-03-008 in patients with advanced cancers that have spread. The goal is to see if the drug is safe, how it behaves in the body, and if it can help fight the cancer.

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 must not have received any cancer treatments within 14 days for small molecule therapies and 28 days for biologic therapies before starting the trial.

What data supports the effectiveness of the drug UCT-03-008 for advanced solid cancers?

Immune checkpoint inhibitors, which are similar to UCT-03-008, have been shown to be safe and effective in treating advanced solid tumors, even in patients with poor health status, with some patients living longer than expected. ^{1 2 3 4 5}

What safety data exists for UCT-03-008 in humans?

The research highlights that targeted therapies and immunotherapies for cancer can have serious side effects, including organ toxicities, which may require intensive care. However, specific safety data for UCT-03-008 is not provided in the available research. ^{6 7 8 9 10}

What makes the drug UCT-03-008 unique for treating advanced solid cancers?

The drug UCT-03-008 is unique because it may involve a novel approach similar to immunotherapy, which can potentially provide a long-lasting immune response against tumor cells, unlike traditional chemotherapy that often leads to resistance and temporary effects. ^{11 12 13 14 15}

Research Team

Alex Garcia

Principal Investigator

TRIO-US

Eligibility Criteria

This trial is for adults with advanced solid tumors that can be measured, who are in fairly good health (able to perform daily activities without significant assistance), and have their major organs working well. Pregnant or breastfeeding women, those not recovered from previous cancer treatments, or anyone who has had certain treatments within the last 14-28 days cannot join.

Inclusion Criteria

Measurable disease, per RECIST v1.1

I am fully active or can carry out light work.

My organs are working well.

Exclusion Criteria

I do not have any serious, uncontrolled illnesses or infections.

I have had cancer before, but it was a long time ago.

I have a history of serious heart problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants receive UCT-03-008 to determine the maximum tolerated dose and recommended phase 2 dose

28 days

Cycle 0 (each cycle is 28 days)

Expansion

Participants receive UCT-03-008 at the recommended phase 2 dose to evaluate safety and efficacy

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Treatment Details

Interventions

• UCT-03-008 (Other)

Trial Overview The study is testing UCT-03-008's safety and how well it works against advanced solid tumors. It will also look at how the body processes the drug. This is the first time humans are being given this treatment to see if it could be a new option for tumor therapy.

Participant Groups

Group I: Expansion as Monotherapy - Part 2 Experimental Treatment 1 Intervention

UCT-03-008 RP2D Expansion

Group II: Dose Finding as Monotherapy - Part 1 Experimental Treatment 1 Intervention

UCT-03-008 Dose Finding

Who Is Running the Clinical Trial?

1200 Pharma, LLC

Lead Sponsor

Trials

2

Recruited

100+

Translational Research in Oncology

Collaborator

Trials

22

Recruited

6,700+

Findings from Research

In a phase II study of 42 heavily pretreated patients with metastatic colorectal cancer, the combination of sorafenib and capecitabine resulted in a median progression-free survival of 6.2 months, indicating a clinically meaningful benefit.

The treatment was associated with manageable toxicity, with hand-foot syndrome being the most common adverse effect, affecting 85.7% of patients, suggesting that while the therapy is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Sorafenib Plus Capecitabine in Previously Treated Metastatic Colorectal Cancer. George, TJ., Ivey, AM., Ali, A., et al.[2021]

In a study of 2438 advanced-stage cancer patients treated with immune checkpoint inhibitors, a higher systemic immune-inflammation index (SII) was linked to lower objective response rates and disease control rates, indicating poorer treatment effectiveness.

High SII levels were associated with significantly shorter overall survival and progression-free survival, suggesting that SII could serve as a valuable non-invasive biomarker for predicting adverse outcomes in cancer patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic immune-inflammation index predicts prognosis and responsiveness to immunotherapy in cancer patients: a systematic review and meta‑analysis. Kou, J., Huang, J., Li, J., et al.[2023]

In a study of 155 patients with advanced solid tumors, those with a better performance status (ECOG PS 0-1) had a median overall survival (OS) of 9.1 months, compared to only 2.9 months for those with poorer performance status (ECOG PS 2-4), indicating that performance status significantly impacts treatment outcomes with immune checkpoint inhibitors (ICIs).

Despite having a poor performance status, 27.3% of patients in the study were still alive after one year, and the treatment was generally well-tolerated, with 84.6% of patients experiencing no severe toxicities, suggesting that ICIs can be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. Kapoor, A., Noronha, V., Patil, VM., et al.[2023]

In a phase II clinical trial involving 60 patients with advanced solid tumors, the combination of radiotherapy, liposomal irinotecan, camrelizumab, and anti-angiogenic therapy resulted in an objective response rate (ORR) of 34.6% and a disease control rate (DCR) of 82.7%, indicating promising anti-tumor activity.

The treatment was generally well tolerated, with 91.7% of patients experiencing treatment-related adverse events, the most common being lymphopenia, anemia, and leukopenia, suggesting that while side effects were prevalent, the combination therapy was manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, single-arm, phase II study (CAP) of radiotherapy plus liposomal irinotecan followed by camrelizumab and anti-angiogenic treatment in advanced solid tumors. Shen, J., Yan, J., Du, J., et al.[2023]

Sipuleucel-T treatment provides a significant survival benefit for patients with metastatic castrate-resistant prostate cancer, especially in those with a lower disease burden.

Most side effects from sipuleucel-T are manageable infusion-related reactions that are short-lived, allowing for the possibility of subsequent therapies after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T for the Treatment of Patients With Metastatic Castrate-resistant Prostate Cancer: Considerations for Clinical Practice. Pieczonka, CM., Telonis, D., Mouraviev, V., et al.[2020]

Emerging cancer therapies, such as monoclonal antibodies and immune effector cell therapies, can lead to serious adverse effects like cytokine release syndrome, which is the most common toxicity and can necessitate ICU admission.

Management of these toxicities often requires a multidisciplinary approach and may involve supportive care, corticosteroids, and immune suppressants, highlighting the need for standardized treatment protocols to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical Care Management of Toxicities Associated With Targeted Agents and Immunotherapies for Cancer. Gutierrez, C., McEvoy, C., Munshi, L., et al.[2021]

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

In a review of 8 randomized controlled trials involving 3,455 patients with advanced gastric cancer, S-1 was associated with fewer severe adverse events compared to 5-fluorouracil (5-FU), particularly showing lower rates of stomatitis, hypokalemia, mucosal inflammation, and hypophosphatemia.

Both S-1 and 5-FU have side effects, but the findings suggest that S-1 may be a safer option for patients, highlighting the need for healthcare providers to monitor and manage adverse events effectively to enhance patient compliance and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 and 5-Fluorouracil-related adverse events in patients with advanced gastric cancer: A meta-analysis. Hu, Q., Xu, J., Ke, J., et al.[2023]

Modern multimodal tumor therapies, which include radiotherapy, chemotherapy, immunotherapy, and targeted therapies, can lead to significant acute and long-lasting side effects that negatively impact patients' quality of life and survival.

The paper highlights the need for better characterization of side effects from newly approved therapies and provides recommendations for monitoring and managing these effects in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. Rassaf, T., Totzeck, M., Backs, J., et al.[2021]

In a systematic review of eight randomized controlled trials involving targeted therapies for RAS wild-type metastatic colon cancer, bevacizumab was associated with a significantly higher risk of serious hypertension, while panitumumab showed a markedly elevated risk of serious thromboembolism (RR 3.65).

Panitumumab-based chemotherapy also presented a higher risk of serious dermatological and renal toxicities compared to cetuximab, including skin toxicity (RR 15.22), mucositis (RR 3.18), hypomagnesemia (RR 20.10), and dehydration (RR 2.81).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis. Choi, YJ., Choi, CY., Rhie, SJ., et al.[2023]

Immunotherapy offers a promising alternative to traditional chemotherapy for advanced solid tumors, as it can generate a long-lasting immune response that may completely eradicate tumor cells rather than just temporarily killing them.

Monoclonal antibodies like ipilimumab and vaccines like sipuleucel-T have shown efficacy in treating specific cancers, such as metastatic melanoma and advanced prostate cancer, and there is growing interest in applying immunotherapy to other solid tumors, potentially in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014. Ascierto, PA., Addeo, R., Cartenì, G., et al.[2023]

The combination of regorafenib, ipilimumab, and nivolumab (RIN) was found to be safe and effective for treating patients with microsatellite stable (MSS) metastatic colorectal cancer, with a recommended phase 2 dose (RP2D) established at 80 mg of regorafenib daily, showing an overall response rate of 27.6%.

In patients without liver metastases, the treatment showed even better outcomes, with a response rate of 36.4% and a median overall survival of over 22 months, indicating that this combination therapy could be a promising option for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy: A Phase 1 Nonrandomized Clinical Trial. Fakih, M., Sandhu, J., Lim, D., et al.[2023]

Checkpoint blockade immunotherapy is effective for only 5% of patients with metastatic colorectal cancer, particularly those with microsatellite instability, while tumors with stable microsatellites typically do not respond to immunotherapy.

A recent clinical trial showed that combining two chemotherapies with two immunotherapies can enhance immune system activation at the tumor site, leading to significant clinical benefits and identifying biomarkers like CTLA-4 expression that predict response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CTLA-4: a possible solution for microsatellite-stable colorectal cancer. Ghiringhelli, F., Thibaudin, M.[2023]

In a study of 164 patients with advanced sarcoma, genomic profiling identified relevant alterations in 67% of patients, highlighting the complexity of these tumors and the potential for targeted molecular-based therapies (MBT).

While MBT was recommended for 47 patients and initiated for 13, only one patient showed an objective response, suggesting that current molecular profiling strategies may not be beneficial for routine clinical practice and need further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial. Arnaud-Coffin, P., Brahmi, M., Vanacker, H., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Activity of Sorafenib Plus Capecitabine in Previously Treated Metastatic Colorectal Cancer. [2021]

2. Italy pubmed.ncbi.nlm.nih.gov

Systemic immune-inflammation index predicts prognosis and responsiveness to immunotherapy in cancer patients: a systematic review and meta‑analysis. [2023]

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

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Multicenter, single-arm, phase II study (CAP) of radiotherapy plus liposomal irinotecan followed by camrelizumab and anti-angiogenic treatment in advanced solid tumors. [2023]

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

Sipuleucel-T for the Treatment of Patients With Metastatic Castrate-resistant Prostate Cancer: Considerations for Clinical Practice. [2020]

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

Critical Care Management of Toxicities Associated With Targeted Agents and Immunotherapies for Cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. [2020]

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

S-1 and 5-Fluorouracil-related adverse events in patients with advanced gastric cancer: A meta-analysis. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014. [2023]

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

Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy: A Phase 1 Nonrandomized Clinical Trial. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Targeting CTLA-4: a possible solution for microsatellite-stable colorectal cancer. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes. [2022]

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

Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial. [2023]