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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, YL-13027, combined with chemotherapy drugs gemcitabine and nab-paclitaxel, to assess its safety for people with pancreatic cancer. It aims to evaluate how well these medications work together. The trial consists of two parts: one to determine the right dose and another to test this dose in more participants. Suitable candidates have metastatic pancreatic cancer that did not respond to one prior treatment and are experiencing active symptoms. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that YL-13027 has been safe in animal studies, particularly in mice with colon cancer. It supported the immune system without causing major side effects. However, information about its effects on humans remains limited, as testing is still in the early stages.

For gemcitabine and nab-paclitaxel, more is known about their safety. Studies have found that these drugs, when used together, can extend the lives of people with pancreatic cancer. They are generally safe, but like all chemotherapy, they can cause side effects such as tiredness, low blood counts, and hair loss.

In summary, the safety of gemcitabine and nab-paclitaxel is well-established, while YL-13027 is still under study to better understand its effects on humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about YL-13027 because it represents a promising innovation in treating pancreatic cancer. Unlike traditional treatments like gemcitabine and nab-paclitaxel, which are chemotherapy agents, YL-13027 is a novel compound being investigated for its potential to enhance the effectiveness of these standard drugs. This combination could offer a more potent approach by possibly targeting the cancer cells more effectively. By integrating YL-13027 with existing therapies, researchers hope to improve outcomes for patients battling this aggressive cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that using gemcitabine and nab-paclitaxel together is promising for treating pancreatic cancer. Studies have found that this combination helps people live longer and slows cancer growth by about 31%. In this trial, participants will receive YL-13027 with gemcitabine and nab-paclitaxel. Early animal research indicated that YL-13027 is safe and enhances the immune system's ability to fight tumors. Although limited information exists on YL-13027 in humans, these findings suggest it could be beneficial when combined with gemcitabine and nab-paclitaxel. The trial aims to determine if adding YL-13027 can enhance the current treatment's effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Jordi Rodon Ahnert

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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]

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]

Citations

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Gemcitabine Therapy in Patients with Advanced Pancreatic ... This study demonstrated results of the low toxicity and the good compliance of gemcitabine treatment in patients with advanced pancreatic cancer.

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.22.02777

Improvements in Survival and Clinical Benefit With ... The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. Conclusion. This study ...

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Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as ... Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304369

Increased Survival in Pancreatic Cancer with nab ... The improvement in progression-free survival corresponded to a 31% reduction in the risk of progression or death with nab-paclitaxel plus gemcitabine, as ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14601-2

Efficacy of second-line treatment for gemcitabine-refractory ... This study aimed to compare the benefits and identify the best second-line treatment regimen for gemcitabine-refractory unresectable ...

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The efficacy and safety of gemcitabine-based combination ... Our study supported that GEM-based combination therapy was more beneficial to improve patient's survival than GEM alone, while there was no additional benefits ...

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The clinical outcomes of adjuvant gemcitabine plus S-1 in ... The 2-year survival rate was 27.3% in the gemcitabine monotherapy group, compared to 67.3% in the GS combination group in the Stage II and III ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/1120009X.2023.2190712

Clinical outcome and safety profile of metastatic pancreatic ... It has been reported that the five-year survival rate is less than 8% for metastatic pancreatic cancer (mPC) [Citation4]. The optimal regimen is not well ...