Adagloxad Simolenin + OBI-821 for Triple Negative Breast Cancer

Not currently recruiting at 174 trial locations

Overseen By OBI Pharma CT.gov Assistant

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: OBI Pharma, Inc

Must be taking: Taxane, Anthracycline

Must not be taking: Corticosteroids, Anticancer vaccines

Disqualifiers: Metastatic disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 100 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with Triple Negative Breast Cancer (TNBC). The researchers aim to determine if adding two new drugs, adagloxad simolenin (a cancer vaccine) and OBI-821, to the standard treatment can improve outcomes for patients with high-risk, early-stage TNBC. Eligible participants should have TNBC that has not spread to other parts of the body and must have completed standard chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain cancer treatments other than the ones allowed in the study, and you should not be on high-dose steroids. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of adagloxad simolenin (OBI-822) and OBI-821 was tested for safety in earlier studies. In one study, patients generally handled the treatments well. Some experienced mild side effects, such as redness at the injection site and flu-like symptoms, but serious side effects were rare.

These results suggest that the treatment is safe for most people. The current trial is in a later stage, indicating that earlier tests showed the treatment to be well-tolerated. It is always advisable to consult with a healthcare provider for more personalized information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Adagloxad Simolenin (OBI-822) combined with OBI-821 for treating triple negative breast cancer because it introduces a novel approach to fighting this aggressive cancer type. Unlike traditional chemotherapy, which broadly attacks both cancerous and healthy cells, this treatment aims to harness the immune system by using a unique vaccine-like mechanism. The combination works by stimulating the body's immune response specifically against cancer cells, potentially offering a more targeted and less toxic alternative to standard chemotherapy. This innovative approach could lead to more effective and manageable treatments for patients who often have limited options.

What evidence suggests that adagloxad simolenin + OBI-821 could be an effective treatment for triple negative breast cancer?

Research shows that a treatment combining adagloxad simolenin and OBI-821 may help treat triple-negative breast cancer (TNBC). In this trial, some participants will receive this combination alongside standard of care (SOC) treatment. Earlier studies found that this treatment boosts the body's immune system by increasing certain antibodies, called IgM and IgG, which help fight cancer cells. The treatment targets a specific marker called Globo H, often found on TNBC cancer cells. Early results suggest that patients might experience better outcomes with this treatment. Overall, it appears promising as an addition to standard care for those with high-risk TNBC. ^{1 2 3 4 6}

Who Is on the Research Team?

Hope Rugo, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for high-risk, early-stage breast cancer patients with Globo H Positive Triple Negative Breast Cancer (TNBC). Participants must have completed standard chemotherapy, have no metastatic disease or other cancers in the last 5 years, and not be on immunosuppressive therapy. They should also agree to use effective contraception.

Inclusion Criteria

I am not able to have children or I have a negative pregnancy test.

My breast cancer is triple-negative, not responding to hormones or HER2 treatments.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

My cancer has spread to other parts of my body.

I have not taken any corticosteroids by mouth or injection in the last 2 weeks.

You are allergic to any of the ingredients in the study drug or have had a severe allergic reaction to fusion proteins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adagloxad simolenin combined with OBI-821 for up to 21 subcutaneous injections over a period of 100 weeks, in conjunction with standard of care treatment

100 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and survival outcomes

7 years

What Are the Treatments Tested in This Trial?

Interventions

• Adagloxad Simolenin (OBI-822)
• OBI-821

Trial Overview The GLORIA study tests adagloxad simolenin (OBI-822)/OBI-821 as an additional treatment after surgery for TNBC. It's compared against standard care treatments to see if it improves outcomes. Patients are randomly assigned to either the new drug combo or standard care.

How Is the Trial Designed?

Group I: Adagloxad simolenin + OBI-821 in conjunction with SOC Experimental Treatment 3 Interventions

Participants will be administered adagloxad simolenin combined with OBI-821 for up to a total of 21 subcutaneous injections over a period of 100 weeks. Patient will also receive standard of care (SOC) treatment.

Group II: Standard of Care treatment Active Control 2 Interventions

Study visit intervals will be identical to those in Arm 1. Patient will receive standard of care (SOC) treatment.

Who Is Running the Clinical Trial?

OBI Pharma, Inc

Lead Sponsor

Trials

9

Recruited

1,500+

Published Research Related to This Trial

In a phase II trial involving 349 patients with metastatic breast cancer, the treatment with adagloxad simolenin (AS/OBI-821) did not show a significant improvement in progression-free survival (PFS) compared to placebo, with median PFS of 7.6 months versus 9.2 months respectively.

However, patients with a strong immune response (anti-Globo H IgG titer ≥1:160) who received AS/OBI-821 experienced significantly longer median PFS of 11.1 months, suggesting that immune response may be a key factor in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. Huang, CS., Yu, AL., Tseng, LM., et al.[2021]

A novel oncolytic virus-infected cell vaccine (ICV) using a prime-boost strategy showed improved survival in mice with aggressive triple negative breast cancer (TNBC), indicating potential efficacy for this hard-to-treat cancer subtype.

Combining early surgical resection of tumors with the prime-boost vaccination significantly enhanced overall survival and immune memory responses, suggesting a promising therapeutic approach for TNBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterologous prime-boost cellular vaccination induces potent antitumor immunity against triple negative breast cancer. Niavarani, SR., St-Cyr, G., Daniel, L., et al.[2023]

In a phase II trial, two patients with chemotherapy-refractory ovarian clear cell carcinoma (CCC) showed significant clinical responses to a GPC3-derived peptide vaccine, indicating its potential as an effective immunotherapy.

Both patients experienced disease stabilization for over a year, suggesting that GPC3 peptide-based immunotherapy may significantly prolong overall survival in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant clinical response of progressive recurrent ovarian clear cell carcinoma to glypican-3-derived peptide vaccine therapy: two case reports. Suzuki, S., Shibata, K., Kikkawa, F., et al.[2021]

In a study involving 171 patients with ovarian cancer, the combination of a polyvalent vaccine conjugate with the adjuvant OPT-821 did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to OPT-821 alone, with a hazard ratio of 0.98.

The treatment was generally well tolerated, with most adverse events being mild, such as injection site reactions (82%) and fever (11%), although some serious toxicities were reported, including grade 4 myelodysplastic syndrome (MDS) in one patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomized, double-blind trial of a polyvalent Vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer who are in second or third complete remission: An NRG Oncology/GOG study. O'Cearbhaill, RE., Deng, W., Chen, LM., et al.[2021]

Ovarian cancer patients often face poor survival rates, with less than 40% surviving past 5 years, highlighting the urgent need for effective treatments like cancer vaccines that can stimulate T cell responses.

Using the murine ID8 ovarian tumor model, the study shows that combining cancer vaccines with standard treatments can enhance overall efficacy, suggesting a promising approach for improving outcomes in ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human. Chiang, CL., Rovelli, R., Sarivalasis, A., et al.[2021]

Adagloxad simolenin (AdaSim), a synthetic vaccine targeting the Globo H antigen, has shown promise in inducing immune responses in patients with metastatic triple-negative breast cancer (TNBC), which is known for its aggressive nature and poor survival rates.

The ongoing phase III GLORIA trial is assessing the safety and efficacy of AdaSim combined with standard care compared to standard care alone, focusing on invasive progression-free survival and other important outcomes like overall survival and quality of life for patients with high-risk, early-stage TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLORIA: phase III, open-label study of adagloxad simolenin/OBI-821 in patients with high-risk triple-negative breast cancer. Rugo, HS., Cortes, J., Barrios, CH., et al.[2022]

A new semi-synthetic saponin adjuvant, GPI-0100, and several combinations of adjuvants were found to be more effective than the previously used QS-21 in enhancing antibody responses against cancer antigens GD3 and MUC1.

The study confirmed that using combinations of immunological adjuvants is crucial for improving immune responses to cancer vaccines, as no T-cell immunity was observed against the antigens, highlighting the need for potent adjuvants to achieve optimal vaccine effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates. Kim, SK., Ragupathi, G., Cappello, S., et al.[2019]

Oncolytic adenoviruses (OAds) represent a promising new therapeutic strategy for treating triple-negative breast cancer (TNBC), which is particularly aggressive and often resistant to standard treatments. Preclinical studies have shown that OAds can selectively target and destroy cancer cells while sparing normal cells, enhancing the potential for improved patient outcomes.

Combining OAds with existing treatments, such as PARP inhibitors like Olaparib and immune checkpoint antibodies, has demonstrated enhanced anti-tumor effects, suggesting that these combinations could lead to more effective therapies for women with TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Triple Negative Breast Cancer With Oncolytic Adenoviruses. Green-Tripp, G., Nattress, C., Halldén, G.[2022]

Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that targets Trop-2 and has shown promising efficacy and tolerability in treating metastatic triple-negative breast cancer (mTNBC), leading to its designation as a breakthrough therapy by the FDA for use as a ≥3rd line treatment.

In clinical trials, sacituzumab govitecan demonstrated significant potential as a novel treatment option for mTNBC, which currently has limited effective therapies, highlighting the need for new approaches to manage this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab for the treatment of triple-negative breast cancer: the poster child of future therapy? Zangardi, ML., Spring, LM., Nagayama, A., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32718986/

Globo H-KLH vaccine adagloxad simolenin (OBI-822) ... This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822)

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03562637

NCT03562637 | Study of Adagloxad Simolenin (OBI-822) ... The GLORIA study is a Phase III, randomized, open-label study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 in the ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS611

A phase 3, randomized, open-label study of the anti-Globo ... A phase 3, randomized, open-label study of the anti-Globo H vaccine adagloxad simolenin/obi-821 in the adjuvant treatment of high-risk, early-stage, Globo H- ...

4. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct03562637

The GLORIA Study: A Phase III, Randomized, Open-Label ... A Phase III, Randomized, Open-Label Study of the Anti-Globo H Vaccine Adagloxad Simolenin OBI-822/OBI-821 in the Adjuvant Treatment of Patients with High-Risk, ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2022-0812

phase III, Open-Label Study of Adagloxad Simolenin/OBI- ... In a phase II study, adagloxad simolenin (AdaSim), a synthetic Globo H conjugate vaccine administered with adjuvant OBI-821, was shown to induce IgM and IgG ...

6. jitc.bmj.com jitc.bmj.com/content/8/2/e000342

Globo H-KLH vaccine adagloxad simolenin (OBI-822) ... This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822)