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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, ALG.APV-527, for individuals with advanced solid tumors such as lung, breast, or prostate cancer. The trial aims to determine a safe dose and assess the treatment's effectiveness. It seeks patients whose cancer has spread, who have not responded to standard treatments, and who have tumors that might respond to this specific treatment. Those meeting these criteria may be suitable candidates for the study. As a Phase 1 trial, this research focuses on understanding the treatment's effects 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 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.

Is there any evidence suggesting that ALG.APV-527 is likely to be safe for humans?

Research shows that ALG.APV-527 is undergoing testing to determine its safety for treating advanced solid tumors. Studies have found that most patients tolerate this treatment well, with few experiencing serious side effects. About 60% of patients maintained stable disease, meaning their cancer did not worsen over time. While these results are encouraging, it is important to remember that this treatment is still being tested to confirm its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ALG.APV-527 is unique because it targets advanced solid tumors with a novel approach by using a bispecific antibody platform. Unlike traditional treatments like chemotherapy, which non-selectively attacks both healthy and cancerous cells, ALG.APV-527 is designed to engage the immune system more precisely by targeting two specific proteins involved in tumor growth and immune evasion. This dual-targeting mechanism aims to enhance the body's natural ability to fight cancer, potentially leading to more effective and personalized treatment outcomes. Researchers are excited about this treatment because it represents a promising step towards more targeted cancer therapies with potentially fewer side effects.

What evidence suggests that ALG.APV-527 might be an effective treatment for advanced cancer?

Research shows that ALG.APV-527, the investigational treatment in this trial, may help treat advanced solid tumors. In earlier studies, 56% of patients with evaluable results had stable disease, meaning their cancer did not worsen during treatment. This is crucial for patients with limited treatment options. ALG.APV-527 boosts the body's immune response specifically in the tumor, aiding in the fight against cancer. Early findings suggest it is both tolerable and potentially effective for tumors that may have the 5T4 antigen, which is linked to some cancers. These initial results offer hope for patients seeking new treatment options. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05934539

NCT05934539 | ALG.APV-527 First-in-human Study This first-in-human study is an open-label, multicenter, Phase 1 study with the aim to assess safety and tolerability and preliminary anti-tumor activity of ALG ...

2. aptevotherapeutics.gcs-web.com aptevotherapeutics.gcs-web.com/news-releases/news-release-details/first-class-bispecific-antibody-algapv-527-meets-important-trial

First-in-Class Bispecific Antibody, ALG.APV-527, Meets ... Among evaluable patients, 56% (9/16) achieved stable disease in this monotherapy trial. A colon cancer patient remained on study with stable ...

3. alligatorbioscience.se alligatorbioscience.se/en/research-and-development/pipeline/alg-apv-527/

ALG.APV-527 APV-527 selectively enhances T cell responses within the tumor. In November 2022, consolidated data was published in Molecular Cancer Therapeutics1, confirming ...

4. urologytimes.com urologytimes.com/view/alg-apv-527-shows-initial-promise-in-solid-tumors-including-gu-cancers

ALG.APV-527 shows initial promise in solid tumors ... The bispecific conditional 4-1BB agonist ALG.APV-527 has demonstrated tolerability and preliminary efficacy in patients with advanced solid tumors.

5. firstwordpharma.com firstwordpharma.com/story/5935402

Aptevo Therapeutics Reports 2024 Financial Results And ... APV-527 Phase 1 dose escalation study evaluating the drug for the treatment of multiple solid tumor types likely to express tumor antigen 5T4.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02253-1/fulltext

668P First-in-human phase I dose escalation study of ALG. ... APV-527, a 5T4 tumor antigen-conditional 4-1BB bispecific antibody, in patients with advanced solid tumors, demonstrates positive safety, signals of biological ...

7. aptevotherapeutics.com aptevotherapeutics.com/pipeline/alg-apv-527/

Aptevo Therapeutics | ALG.APV-527 The trial enrolled adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 was administered intravenously once ...

8. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A772

673 Preliminary results from a phase I dose escalation ... APV-527, a 5T4 x 4–1BB bispecific antibody, in patients with advanced solid tumors demonstrate favorable safety and biological activity. Author ...

9. aptevotherapeutics.gcs-web.com aptevotherapeutics.gcs-web.com/news-releases/news-release-details/aptevo-therapeutics-and-alligator-bioscience-announce-data-phase

Aptevo Therapeutics and Alligator Bioscience Announce Data ... APV-527 showing a positive safety profile with 60% of evaluable patients achieving stable disease, meaning not progressing for variable time frames including ...