AP160-Complex for Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Anticancer, Corticosteroids

Disqualifiers: Pregnancy, HIV, Autoimmune, Cardiac, others

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

Compensation: Varies

Number of Visits: 8

Duration: 28 days (Cycle 1)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination, AP160-complex, to determine the safest dose and identify side effects in people with advanced or metastatic solid tumors. The treatment combines a chemotherapy drug, nab-paclitaxel (also known as ABI-007, nanoparticle albumin-bound paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxel, Abraxane, or Pazenir), which stops tumor growth, with an immunotherapy drug, STI-3031, which helps the immune system fight cancer. The trial seeks participants who have previously tried at least one other cancer treatment without success. It may suit those with advanced cancer that has spread and who have no other treatment options. 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 therapy.

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 anti-cancer therapy or investigational agents within 4 weeks prior to registration, and you must be off systemic corticosteroids for at least 2 weeks before registration, unless you are on a low dose for chronic conditions. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the AP160-complex is likely to be safe for humans?

Research shows that nab-paclitaxel is usually well-tolerated and safe in various cancer treatments. Common side effects include low white blood cell counts, hair loss, and tiredness, but these can usually be managed.

For STI-3031, less information is available. This experimental treatment helps the immune system find and attack cancer cells. Previous studies in other conditions suggest it may have manageable side effects, but more data is needed.

Since this trial is in an early stage, it focuses on understanding safety and side effects. The treatment hasn't been widely tested in people yet, so safety information is limited. Participants in this trial will help gather important information about how well the treatment is tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the AP160-complex for advanced cancer because it combines nab-paclitaxel with STI-3031, offering a potentially new approach to treatment. Unlike traditional therapies that might focus solely on one pathway, this combination targets multiple cancer growth mechanisms, which could enhance its effectiveness. Additionally, the AP160-complex is administered intravenously, allowing for precise dosing and direct delivery to the bloodstream, potentially improving outcomes and minimizing side effects compared to some oral medications. These features make it a promising candidate for offering advanced cancer patients a new line of defense.

What evidence suggests that the AP160-complex could be effective for advanced cancer?

Research has shown that nab-paclitaxel effectively treats various cancers, such as advanced breast cancer and pancreatic cancer. Studies indicate that it can slow tumor growth and extend survival. Nab-paclitaxel works by preventing cancer cells from growing and spreading.

STI-3031, an immunotherapy treatment, may help the body's immune system fight cancer cells. It has been studied in individuals with melanoma, a type of skin cancer, and early results suggested its effectiveness. In this trial, nab-paclitaxel and STI-3031 combine to form the AP160-complex, which aims to stop cancer cell growth and enhance the immune system's response to cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including melanoma, who have already tried at least one systemic therapy. Participants must provide consent and a tissue sample for research. There's no limit to prior treatments but the cancer should be non-neurological and without curative options.

Inclusion Criteria

My melanoma cannot be removed with surgery and is stage IV.

Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)

For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment

Exclusion Criteria

I am not willing to use birth control during the study.

I have not fully recovered from my last surgery.

I have had a severe reaction to immune therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI scan, blood sample collection

Treatment

Patients receive AP160-complex IV with dose-escalation and dose-expansion cohorts

28 days (Cycle 1)

Regular visits for MRI scans, tissue biopsies, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days after last dose

Re-evaluation every 8 weeks

Long-term follow-up

Monitoring for disease progression/recurrence

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Nab-paclitaxel
• STI-3031

Trial Overview The trial tests the safety and optimal dose of AP160-complex, a new drug combining chemotherapy (nab-paclitaxel) and immunotherapy (STI-3031). It aims to see if this complex can better halt tumor growth compared to standard therapies in patients with advanced or metastatic solid tumors.

How Is the Trial Designed?

Group I: Treatment (AP160-complex) Experimental Treatment 5 Interventions

Patients receive AP160-complex IV on study. Patients in the dose-escalation cohort undergo computed tomography/magnetic resonance imaging (MRI) scans, tissue biopsies, and collection of blood samples throughout the trial. Patients in the dose-expansion cohort undergo MRI scan during screening, collection of blood samples during screening and on study, and tissue biopsies throughout the trial.

Nab-paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Approved in European Union as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Approved in Canada as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

ABI-007, a novel nanoparticle formulation of paclitaxel, demonstrated a significant overall response rate of 48% in treating metastatic breast cancer, with even higher rates of 64% for first-line therapy, indicating its efficacy in this patient population.

The treatment was well-tolerated, with no severe hypersensitivity reactions reported despite the absence of premedication, and typical toxicities associated with paclitaxel, such as neutropenia and sensory neuropathy, were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. Ibrahim, NK., Samuels, B., Page, R., et al.[2022]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

NAB-paclitaxel at a dose of 125 mg/m² was well tolerated in patients with stage IV non-small-cell lung cancer, with no hypersensitivity reactions reported and a maximum-tolerated dose established without significant dose-limiting toxicities.

The treatment showed promising efficacy, with a 30% objective response rate, a median time to progression of 5 months, and a median overall survival of 11 months, indicating its potential as a viable single-agent therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. Rizvi, NA., Riely, GJ., Azzoli, CG., et al.[2015]

ABI-007, a novel formulation of paclitaxel, can be safely administered at higher doses than traditional paclitaxel formulations, with maximum-tolerated doses of 100 mg/m² for heavily pretreated patients and 150 mg/m² for lightly pretreated patients.

The study showed partial antitumor responses in patients with breast, lung, and ovarian cancers, indicating that ABI-007 may be effective even in those previously treated with standard paclitaxel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. Nyman, DW., Campbell, KJ., Hersh, E., et al.[2022]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

ABI-007, a solvent-free albumin-bound paclitaxel, showed significantly higher response rates (33% vs. 19%) and longer time to tumor progression (23.0 weeks vs. 16.9 weeks) compared to standard paclitaxel in a phase III study with 454 patients.

ABI-007 had a lower incidence of severe neutropenia (9% vs. 22%) and did not require premedication, indicating a better safety profile, although it was associated with a higher rate of manageable sensory neuropathy (10% vs. 2%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Gradishar, WJ., Tjulandin, S., Davidson, N., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9016319/

A Real-World Efficacy of Nab-Paclitaxel Monotherapy in ... In conclusion, this real-world data shows that nab-paclitaxel is an effective treatment option in metastatic breast cancer. Nab-paclitaxel was well tolerated ...

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2720743/

Albumin-bound formulation of paclitaxel (Abraxane® ABI- ... The overall response rate (at a dose of 300 mg/m2 every 3 weeks) was 48% for all patients and 64% for patients in first-line therapy. Time to tumor progression ...

4. ijmio.com ijmio.com/real-world-study-on-the-effect-of-nab-paclitaxel-treatment-on-clinical-outcomes-and-laboratory-parameters-in-patients-across-metastatic-tumor-sites/

Real-world study on the effect of nab-paclitaxel treatment ... Nab-paclitaxel showed manageable tolerability and favorable response rates in metastatic cancer patients. It is widely used beyond approved indications.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02103062?term=Paclitaxel&viewType=Table&rank=2&tab=results

Phase 2 Study With Abraxane (Nab®Paclitaxel) in ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

6. nature.com nature.com/articles/s41598-025-16848-y

Distinct safety profiles of albumin-bound nab-paclitaxel and ... Both Nab-paclitaxel and paclitaxel were primarily indicated for pancreatic cancer, a finding that aligns with their clinical usage in advanced ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/021660s047lbl.pdf

ABRAXANE (paclitaxel) Label - accessdata.fda.gov Non-Small Cell Lung Cancer. Adverse reactions were assessed in 514 ABRAXANE/carboplatin-treated patients and 524 paclitaxel injection/carboplatin-treated.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11599493/

Safety and efficacy of generic nab-paclitaxel-based therapy ... This study demonstrates a promising safety and efficacy of generic nab-paclitaxel-based regimens for Chinese patients with malignancies in a real-world setting.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02267707

Pharmacokinetic and Safety Study of Nab®-Paclitaxel (ABI ... The purpose of this study is to determine the safety and pharmacokinetic profile of nab®-paclitaxel (ABI-007) plus gemcitabine in subjects with advanced ...

10. abraxanepro.com abraxanepro.com/important-safety-information

ABRAXANE® Safety Information Learn about indications and safety information for ABRAXANE®. See full prescribing info and BOXED WARNINGS on neutropenia.