YL-13027 + Chemotherapy for Pancreatic Cancer

Overseen By Jordi Rodon Ahnert, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors/inducers

Disqualifiers: Brain metastases, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does prohibit the use of strong CYP3A inhibitors or inducers within 14 days before starting the study treatment and during the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the drug YL-13027 + Chemotherapy for Pancreatic Cancer?

Research shows that combining nab-paclitaxel (a form of paclitaxel bound to a protein called albumin) with gemcitabine significantly improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This suggests that the combination of these drugs can be effective in treating pancreatic cancer. ^{1 2 3 4 5}

Is the combination of YL-13027 and chemotherapy safe for treating pancreatic cancer?

The combination of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine has been shown to be generally safe for treating pancreatic cancer, with manageable side effects like neutropenia (low white blood cell count) and peripheral neuropathy (nerve damage causing tingling or numbness). These side effects were mostly mild to moderate and often resolved with dose adjustments. ^{3 5 6 7 8}

What makes the drug YL-13027 + Chemotherapy unique for pancreatic cancer?

The combination of YL-13027 with chemotherapy drugs gemcitabine and nab-paclitaxel is unique because it may enhance the effectiveness of treatment by overcoming resistance to gemcitabine, a common issue in pancreatic cancer, potentially leading to better outcomes. ^{4 5 8 9 10}

What is the purpose of this trial?

To learn if the study drug, YL-13027, is safe to give in combination with gemcitabine and nab-paclitaxel to participants with pancreatic cancer.

Research Team

Jordi Rodon Ahnert

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals with metastatic pancreatic cancer that hasn't responded to previous treatments. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments.

Inclusion Criteria

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

My cancer did not respond to one previous treatment in its advanced stage.

My organs and bone marrow are functioning well.

Exclusion Criteria

Mean QTcF >470 ms at screening

Participants who are pregnant or breastfeeding or expecting to conceive within the projected duration of the study

I have been treated with a TGF-β pathway-targeted agent before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants will be assigned to a dose level of YL-13027 in combination with gemcitabine and nab-paclitaxel based on when they join the study

8-12 weeks

Dose Expansion

Participants will receive YL-13027 in combination with gemcitabine and nab-paclitaxel at the recommended dose found in the Dose Escalation part

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• Nab-paclitaxel
• YL-13027

Trial Overview The study is testing the safety of a new drug called YL-13027 when given alongside two chemotherapy drugs, Gemcitabine and Nab-paclitaxel, in patients with advanced pancreatic cancer.

Participant Groups

Group I: Dose Expansion Experimental Treatment 3 Interventions

Participants will receive YL-13027 in combination with gemcitabine and nab-paclitaxel at the recommended dose that was found in the Dose Escalation part.

Group II: Dose Escalation Experimental Treatment 3 Interventions

Participants will be assigned to a dose level of YL-13027 in combination with gemcitabine and nab-paclitaxel based on when you join this study.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

280Bio Inc

Collaborator

Trials

1

Recruited

60+

Findings from Research

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

Gemcitabine-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully developed and showed a favorable controlled release, with an encapsulation rate of approximately 83% and a particle size of about 150 nm.

In vivo studies demonstrated that Gem-HSA-NPs significantly inhibited tumor growth in pancreatic cancer while exhibiting lower toxicity compared to other treatment groups, indicating their potential as a safer and more effective delivery method for gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. Yu, X., Di, Y., Xie, C., et al.[2022]

In a study involving 221 patients with metastatic pancreatic ductal adenocarcinoma and poor performance status, the combination of NAB-paclitaxel and gemcitabine was found to be well tolerated, with manageable side effects such as anemia and neutropenia.

Both dosing regimens of NAB-paclitaxel (100 mg/m2 and 125 mg/m2) showed similar efficacy, with comparable response rates and median progression-free survival, indicating that this treatment is effective for fragile patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. Macarulla, T., Pazo-Cid, R., Guillén-Ponce, C., et al.[2022]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

Nab-paclitaxel, when combined with gemcitabine, significantly improves overall survival in adults with metastatic pancreatic cancer, reducing the risk of death by 28% compared to gemcitabine alone, based on a multinational phase III study.

The treatment has a manageable safety profile, with most adverse events being grade 3 or lower, and common side effects like neutropenia and peripheral neuropathy are generally reversible with dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel: a review of its use for the first-line combination treatment of metastatic pancreatic cancer. Hoy, SM.[2021]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a phase II trial involving 61 patients with borderline resectable pancreatic cancer, the neoadjuvant therapy of nab-paclitaxel plus gemcitabine resulted in a median overall survival of 25.2 months and a median recurrence-free survival of 12.3 months, indicating promising efficacy.

The treatment had a high resection rate of 73.8% and an R0 resection rate of 63.9%, but it also presented significant safety concerns, with 73.8% of patients experiencing grade 3/4 adverse events, highlighting the need for careful patient selection, especially for those with prior lung issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). Okada, KI., Kimura, K., Yamashita, YI., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

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

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. [2022]

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

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. [2022]

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

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. [2022]

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

Albumin-bound paclitaxel: a review of its use for the first-line combination treatment of metastatic pancreatic cancer. [2021]

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

nab-Paclitaxel for the treatment of pancreatic cancer. [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). [2023]

10. Greece pubmed.ncbi.nlm.nih.gov

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death. [2022]