ALG.APV-527 for Advanced Cancer

Overseen By Caroline Taromino, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Aptevo Therapeutics

Must not be taking: Immunotherapy, Steroids, Anticonvulsants, others

Disqualifiers: CNS disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 3

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, ALG.APV-527, in adults with advanced solid tumors who have no other effective treatments. The drug is given through an IV to find the safest dose. Researchers aim to see if the drug is safe and can help shrink tumors.

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 cannot have received certain cancer treatments or investigational agents within a specific time before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What makes the treatment ALG.APV-527 unique for advanced cancer?

ALG.APV-527 is unique because it likely involves a novel approach using adeno-associated virus (AAV) vectors for targeted delivery of immune checkpoint inhibitors (ICIs) directly to tumor cells, potentially reducing side effects and enhancing the effectiveness of the treatment compared to traditional methods. ^{1 2 3 4 5}

Eligibility Criteria

Adults with advanced solid tumors that have failed standard treatments or for whom no effective therapy exists. They must be over 18, have a life expectancy of at least 3 months, and agree to use effective birth control. Specific cancers include NSCLC, breast cancer, ovarian cancer among others. Participants need adequate organ function and measurable lesions by CT/MRI.

Inclusion Criteria

Have provided signed informed consent form (ICF) for participation in the study

I have one of the listed types of cancer.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had immunotherapy or experimental drugs in the last 28 days.

I have a history of brain or spinal cord disease.

In the opinion of the treating Investigator, has any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Dose Escalation

Participants receive ALG.APV-527 in increasing dose levels to determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D)

28 days per cohort

Multiple visits (in-person) per cohort

Dose Expansion

Participants receive ALG.APV-527 at the RP2D to further evaluate safety and clinical activity

24 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• ALG.APV-527

Trial Overview The trial is testing ALG.APV-527 in patients with advanced solid tumors likely to express the 5T4 antigen. It's an open-label study with two parts: dose escalation (about 36 patients) and dose expansion (about 20 patients), focusing on safety and optimal dosing.

Participant Groups

Group I: ALG.APV-527 Experimental Treatment 1 Intervention

Part 1 Dose Escalation using ALG.APV-527 doses with a starting dose of 0.1 mg/kg and projected 6 dose cohorts will be explored to determine the MTD and/or the RP2D. Part 1 consists of a 3 + 3 dose-escalation examination of ALG.APV-527 single agent therapy in adult patients with RECIST Version1.1-measurable advanced solid tumors. Part 2 Dose Expansion with ALG.APV-527 based on RP2D determined during Dose Escalation.

Who Is Running the Clinical Trial?

Aptevo Therapeutics

Lead Sponsor

Trials

9

Recruited

490+

Alligator Bioscience AB

Industry Sponsor

Trials

5

Recruited

230+

Findings from Research

AAV-2 infection significantly enhances the effectiveness of chemotherapeutic drugs like cisplatin in various human tumor cell lines and fresh tumor biopsies, indicating its potential as a sensitizing agent in cancer treatment.

In animal studies, combining AAV-2 infection with chemotherapy resulted in greater tumor reduction compared to chemotherapy alone, suggesting that AAV-2 could improve therapeutic outcomes in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved efficacy of chemotherapy by parvovirus-mediated sensitisation of human tumour cells. Klein-Bauernschmitt, P., von Knebel Doeberitz, M., Ehrbar, M., et al.[2019]

Adeno-associated virus (AAV) vectors are emerging as promising tools for gene therapy, particularly for inherited diseases, due to their excellent safety profiles and the ability to produce them on a large scale.

Current research is exploring the use of AAV vectors in cancer gene therapy, aiming to develop novel treatment strategies that could transition from pre-clinical studies to clinical applications, addressing a significant health challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Clinical Implementation of Adeno-Associated Virus (AAV) Vectors for Cancer Gene Therapy: Current Status and Future Perspectives. Hacker, UT., Bentler, M., Kaniowska, D., et al.[2020]

Recombinant adeno-associated virus 2 (rAAV2) targeting insulin-like growth factor-binding protein 2 (IGFBP-2) significantly inhibited the growth and metastasis of breast cancer cells in vitro and in vivo, demonstrating its potential as a therapeutic agent for aggressive breast cancer types.

The study found that rAAV2-ZsGreen-shRNA-hIGFBP-2 increased the sensitivity of breast cancer cells to the chemotherapy drug paclitaxel and reduced the invasive ability of these cells, suggesting a mechanism for enhancing treatment efficacy in triple-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated virus type 2-mediated gene transfer of a short hairpin-RNA targeting human IGFBP-2 suppresses the proliferation and invasion of MDA-MB-468 cells. Gao, C., Zhang, RS., Zheng, N., et al.[2021]

Infection with the non-pathogenic adeno-associated virus type 2 (AAV-2) significantly enhances the sensitivity of small cell lung cancer (SCLC) cells to chemotherapy, reducing the number of proliferating cells when combined with drugs like cisplatin and etoposide.

In vivo studies in immunocompromised mice showed that AAV-2 infection led to a more effective reduction in tumor growth compared to chemotherapy alone, suggesting that AAV-2 could be a valuable tool in improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced sensitivity of small cell lung cancer cell lines to cisplatin and etoposide after infection with adeno-associated virus type 2. Hillgenberg, M., Schlehofer, JR., von Knebel Doeberitz, M., et al.[2019]

The study demonstrates that Her2-targeted adeno-associated virus (AAV) vectors can effectively deliver immune checkpoint inhibitors (ICIs) directly to tumor tissues, reducing the presence of these inhibitors in the liver, which may minimize adverse effects.

In mouse models, the use of Her2-AAV for delivering the αPD-1 gene showed promising results, including specific gene delivery to tumors and a potential reduction in tumor growth when combined with chemotherapy, indicating a novel approach to enhance cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-Specific Delivery of Immune Checkpoint Inhibitors by Engineered AAV Vectors. Reul, J., Frisch, J., Engeland, CE., et al.[2020]

References

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

Improved efficacy of chemotherapy by parvovirus-mediated sensitisation of human tumour cells. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Towards Clinical Implementation of Adeno-Associated Virus (AAV) Vectors for Cancer Gene Therapy: Current Status and Future Perspectives. [2020]

3. Greece pubmed.ncbi.nlm.nih.gov

Adeno-associated virus type 2-mediated gene transfer of a short hairpin-RNA targeting human IGFBP-2 suppresses the proliferation and invasion of MDA-MB-468 cells. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Enhanced sensitivity of small cell lung cancer cell lines to cisplatin and etoposide after infection with adeno-associated virus type 2. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Tumor-Specific Delivery of Immune Checkpoint Inhibitors by Engineered AAV Vectors. [2020]