Adagloxad Simolenin + OBI-821 for Triple Negative Breast Cancer
Recruiting in Palo Alto (17 mi)
+138 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a new treatment that combines two substances to help the immune system fight a specific type of high-risk breast cancer. It focuses on patients whose cancer does not respond well to usual treatments.
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.
What data supports the effectiveness of the treatment Adagloxad Simolenin + OBI-821 for Triple Negative Breast Cancer?
The treatment Adagloxad Simolenin + OBI-821 has shown promise in a phase II trial for metastatic breast cancer, where it was assessed for its ability to trigger an immune response against cancer cells. Additionally, similar vaccine approaches using components like QS-21 have been effective in enhancing immune responses in other cancer types, suggesting potential benefits for this treatment.
12345Is the treatment Adagloxad Simolenin + OBI-821 safe for humans?
The ongoing GLORIA phase III trial is evaluating the safety of Adagloxad Simolenin (AdaSim) with OBI-821 in patients with high-risk triple-negative breast cancer, following a phase II study that showed it induced immune responses in patients with metastatic breast cancer. Safety and tolerability are among the secondary endpoints being assessed in this trial.
45678How is the treatment Adagloxad Simolenin + OBI-821 unique for triple negative breast cancer?
Adagloxad Simolenin + OBI-821 is a unique treatment for triple negative breast cancer because it is a vaccine that targets the Globo H antigen, which is overexpressed in some breast cancers, and works by stimulating the immune system to produce antibodies against cancer cells. This approach is different from traditional treatments like chemotherapy, as it aims to harness the body's immune response to fight the cancer.
12679Eligibility Criteria
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.
+15 more
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.
+13 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Adagloxad simolenin + OBI-821 in conjunction with SOCExperimental Treatment3 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 treatmentActive Control2 Interventions
Study visit intervals will be identical to those in Arm 1.
Patient will receive standard of care (SOC) treatment.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nebraska Hematology Oncology PCLincoln, NE
Bons Secours St. Francis Medical Oncology CenterMidlothian, VA
Kaiser Permanente Medical CenterHarbor City, CA
Long Beach Memorial Medical CenterLong Beach, CA
More Trial Locations
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Who Is Running the Clinical Trial?
OBI Pharma, IncLead Sponsor
References
Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. [2021]This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822; a Globo H epitope covalently linked to keyhole limpet hemocyanin (KLH)) with adjuvant OBI-821 in metastatic breast cancer (MBC).
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. [2021]Early-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity.
Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates. [2019]A year ago we described a comparison of 19 immunological adjuvants for their ability to augment antibody and T-cell responses against vaccines containing two cancer antigens, GD3 ganglioside and MUC1 peptide, covalently attached to keyhole limpet hemocyanin (KLH). As in our previous experience, the saponin fraction QS-21 was the most potent single adjuvant but several other adjuvants also had potent adjuvant activity. Induction of an immune response against cancer antigens is generally difficult because these antigens are autoantigens. To get maximal benefit from the adjuvant component of cancer vaccines we have now tested whether combinations of the optimal adjuvants induced an improved immune response compared to QS-21 alone. Since over the intervening year a new semi-synthetic saponin adjuvant (GPI-0100) containing the dodecylamide derivative of hydrolyzed naturally-occurring saponins had become available, this was tested as well. Twelve different adjuvant combinations and GPI-0100 were compared for their ability to augment (1) antibody responses against GD3 and MUC1 and (2) T-cell responses against GD3, MUC1 and KLH. GPI-0100 and five adjuvant combinations were superior to QS-21 alone for induction of IgM and IgG antibodies against MUC1 and/or GD3: QS-21 plus bacterial nucleotide CpG, QS-21 plus monophosphoryl lipid A (MPL), QS-21 plus non-ionic block copolymer CRL-1005, QS-21 plus Titermax and Titermax plus CpG. Antibody responses were documented both by ELISA against purified antigens and by FACS for cell surface reactivity. There was no evidence for T-cell immunity against GD3 or MUC1. The antibody responses against GD3 and MUC1 were, however, strongly correlated with IFN-gamma release and DTH against KLH. These results demonstrate that combinations of immunological adjuvants are able to augment antibody and T-cell responses to these conjugates beyond that attainable with QS-21 alone, and again confirm the absolute necessity of potent adjuvants or adjuvant combinations for optimal immunogenicity with conjugate vaccines.
Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human. [2021]As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC.
Significant clinical response of progressive recurrent ovarian clear cell carcinoma to glypican-3-derived peptide vaccine therapy: two case reports. [2021]Carcinoembryonic antigen glypican-3 (GPC3) is expressed by>40% of ovarian clear cell carcinoma (CCC) and is a promising immunotherapeutic target. We previously reported the safety of and immunological and clinical responses to a GPC3-derived peptide vaccine in a phase I clinical trial of patients with advanced hepatocellular carcinoma (HCC). Although the efficacy of the GPC3-derived peptide vaccine against HCC patients was evaluated, other GPC3-positive cancer patients have not yet been investigated. Therefore, we conducted a phase II trial to evaluate the clinical outcome of ovarian CCC patients treated with a GPC3-derived peptide vaccine. The GPC3 peptide was administered at a dose of 3 mg per body. Patients received an intradermal injection of the GPC3 peptide emulsified with incomplete Freund's adjuvant. Vaccinations were performed biweekly from the first until the 6th injection and were then repeated at 6-week intervals after the 7th injection. Treatment continued until disease progression. We herein present two patients with chemotherapy-refractory ovarian CCC who achieved a significant clinical response in an ongoing trial of a GPC3 peptide vaccine. Case 1, a 42-year-old patient with advanced recurrent ovarian CCC with liver and retroperitoneal lymph node metastases, received the HLA-A24-restricted GPC3 peptide vaccine. Contrast-enhanced CT at week 10 revealed a partial response (PR) using RECIST criteria. Case 2 was a 67-year-old female with multiple lymph node metastases. She was injected with the HLA-A2-restricted GPC3 peptide vaccine. According to RECIST, PR was achieved at week 37. The stabilization of their diseases over one year provided us with the first clinical evidence to demonstrate that GPC3 peptide-based immunotherapy may significantly prolong the overall survival of patients with refractory ovarian CCC.
GLORIA: phase III, open-label study of adagloxad simolenin/OBI-821 in patients with high-risk triple-negative breast cancer. [2022]Triple-negative breast cancer (TNBC) has the highest rate of distant metastasis and poorest overall survival among breast cancer subtypes. 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 anti-Globo H humoral responses in patients with metastatic breast cancer overexpressing the glycosphingolipid Globo H. GLORIA is an ongoing phase III, randomized, open-label clinical trial to evaluate the safety and efficacy of AdaSim and the quality of life (QoL) of patients receiving AdaSim plus standard of care (SOC) versus SOC alone in high-risk, early-stage TNBC. The primary end point is invasive progression-free survival; secondary end points include overall survival, QoL, breast cancer-free interval, distant disease-free survival, safety, and tolerability.
Targeting Triple Negative Breast Cancer With Oncolytic Adenoviruses. [2022]Breast cancer (BC) is the most common cancer globally, accounting for 685,000 deaths in 2020. Triple-negative breast cancers (TNBC) lack oestrogen (ER) and progesterone (PR) hormone receptor expression and HER2 overexpression. TNBC represent 10-15% of all BC with high incidence in women under 50-years old that have BRCA mutations, and have a dismal prognosis. African American and Hispanic women are at higher risk partly due to the common occurrence of BRCA mutations. The standard treatment for TNBC includes surgery, radiotherapy, and chemotherapy although, resistance to all standard-of-care therapies eventually develops. It is crucial to identify and develop more efficacious therapeutics with different mechanisms of action to improve on survival in these women. Recent findings with oncolytic adenoviruses (OAds) may generate a new strategy to improve on the outcomes for women afflicted by TNBC and other types of BC. OAds are genetically engineered to selectively lyse, eliminate and recruit the host antitumour immune responses, leaving normal cells unharmed. The most common modifications are deletions in the early gene products including the E1B55 KDa protein, specific regions of the E1A protein, or insertion of tumour-specific promoters. Clinical trials using OAds for various adenocarcinomas have not yet been sufficiently evaluated in BC patients. Preclinical studies demonstrated efficacy in BC cell lines, including TNBC cells, with promising novel adenoviral mutants. Here we review the results reported for the most promising OAds in preclinical studies and clinical trials administered alone and in combination with current standard of care or with novel therapeutics. Combinations of OAds with small molecule drugs targeting the epidermal growth factor receptor (EGFR), androgen receptor (AR), and DNA damage repair by the novel PARP inhibitors are currently under investigation with reported enhanced efficacy. The combination of the PARP-inhibitor Olaparib with OAds showed an impressive anti-tumour effect. The most promising findings to date are with OAds in combination with antibodies towards the immune checkpoints or expression of cytokines from the viral backbone. Although safety and efficacy have been demonstrated in numerous clinical trials and preclinical studies with cancer-selective OAds, further developments are needed to eliminate metastatic lesions, increase immune activation and intratumoural viral spread. We discuss shortcomings of the OAds and potential solutions for improving on patient outcomes.
Sacituzumab for the treatment of triple-negative breast cancer: the poster child of future therapy? [2019]Label="INTRODUCTION" NlmCategory="BACKGROUND">Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately impacts younger women and is associated with a poor prognosis. Systemic treatment options for metastatic TNBC (mTNBC) are limited to cytotoxic chemotherapy agents with low response rates. This encouraged the clinical development of sacituzumab govitecan (IMMU-132), an antibody-drug conjugate targeting Trop-2, a potential target in epithelial cancer such as TNBC. Areas covered: We summarize the key features, pharmacokinetics, and the safety and efficacy data of sacituzumab govitecan. We also discuss the future directions of this novel therapeutic agent for mTNBC. Expert opinion: Based on the efficacy and tolerability observed in the phase 1/2 clinical trial, sacituzumab govitecan was granted breakthrough therapy designation by the Food and Drug Administration as ≥3rd line therapy for mTNBC. Novel treatment modalities for the management of mTNBC are necessary to improve the care of this aggressive disease. Sacituzumab govitecan represents an important advance in the treatment of mTNBC because of its efficacy and tolerability.
Heterologous prime-boost cellular vaccination induces potent antitumor immunity against triple negative breast cancer. [2023]Triple negative breast cancer (TNBC) is the most aggressive and hard-to-treat subtype of breast cancer, affecting 10-20% of all women diagnosed with breast cancer. Surgery, chemotherapy and hormone/Her2 targeted therapies are the cornerstones of treatment for breast cancer, but women with TNBC do not benefit from these treatments. Although the prognosis is dismal, immunotherapies hold significant promise in TNBC, even in wide spread disease because TNBC is infiltrated with more immune cells. This preclinical study is proposing to optimize an oncolytic virus-infected cell vaccine (ICV) based on a prime-boost vaccination strategy to address this unmet clinical need.