DB-1303 for Solid Cancers
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: DualityBio Inc.
No Placebo Group
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called DB-1303 to see if it is safe for patients with advanced solid tumors that express HER2. The study will begin with lower doses and increase them over time to find the highest dose that patients can handle. This helps determine the best dose for future studies.
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, unresolved toxicities from previous anticancer therapy must be resolved to a certain level before participating.
Is the drug DB-1303 a promising treatment for solid cancers?Yes, DB-1303 is a promising treatment for solid cancers because it uses advanced technology to target cancer cells more effectively. This drug is part of a new approach that aims to improve cancer treatment by focusing on specific markers found on cancer cells, which can help in fighting the disease more efficiently.345714
What safety data exists for DB-1303/BNT323 in solid cancers?The provided research does not contain specific safety data for DB-1303, BNT323, or DB-1303/BNT323 in solid cancers. The articles focus on other treatments and approaches for breast cancer, particularly triple-negative breast cancer, but do not mention DB-1303 or its variants.12101315
What data supports the idea that DB-1303 for Solid Cancers is an effective drug?The available research does not provide any data specifically about DB-1303 for Solid Cancers. Instead, it focuses on other treatments like durvalumab and tremelimumab for different types of cancer, such as non-small-cell lung cancer (NSCLC) and anaplastic thyroid cancer (ATC). These studies show mixed results, with some treatments improving survival in certain cases, but they do not mention DB-1303. Therefore, there is no direct evidence from the provided information to support the effectiveness of DB-1303 for Solid Cancers.6891112
Eligibility Criteria
This trial is for adults with advanced solid tumors that are HER2-positive or express HER2, and have not responded to standard treatments or have no standard options left. Participants must be relatively healthy (ECOG 0-1), have a life expectancy of at least 3 months, a functioning heart (LVEF ≥ 50%), and adequate organ function.Inclusion Criteria
My cancer is HER2-positive or expresses HER2, is advanced, and doesn't respond to standard treatments.
I am fully active or can carry out light work.
Exclusion Criteria
I have a history of serious heart failure or heart rhythm problems needing treatment.
I don't have lasting side effects from cancer treatment worse than mild.
I have active brain tumors.
I have a history of serious lung problems.
I do not have an infection needing IV drugs.
I have HIV with AIDS or active hepatitis.
Treatment Details
The study tests DB-1303's safety and effectiveness in different doses for those with specific types of advanced cancer. It includes other drugs like Itraconazole, Pertuzumab Injection, Ritonavir as part of the treatment regimen in a Phase 1/2a setting.
21Treatment groups
Experimental Treatment
Group I: DB-1303/BNT323 Dose Level 7Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 7 on Day 1 of each cycle Q3W
Group II: DB-1303/BNT323 Dose Level 6Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 6 on Day 1 of each cycle Q3W
Group III: DB-1303/BNT323 Dose Level 5Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 5 on Day 1 of each cycle Q3W
Group IV: DB-1303/BNT323 Dose Level 4Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 4 on Day 1 of each cycle Q3W
Group V: DB-1303/BNT323 Dose Level 3Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 3 on Day 1 of each cycle Q3W
Group VI: DB-1303/BNT323 Dose Level 2Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 2 on Day 1 of each cycle Q3W
Group VII: DB-1303/BNT323 Dose Level 1Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 1 on Day 1 of each cycle Q3W
Group VIII: DB-1303/BNT323 Dose Expansion 9Experimental Treatment1 Intervention
Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 on Day 1 of each cycle Q3W
Group IX: DB-1303/BNT323 Dose Expansion 8Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group X: DB-1303/BNT323 Dose Expansion 7Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XI: DB-1303/BNT323 Dose Expansion 6Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XII: DB-1303/BNT323 Dose Expansion 5Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XIII: DB-1303/BNT323 Dose Expansion 4Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XIV: DB-1303/BNT323 Dose Expansion 3Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XV: DB-1303/BNT323 Dose Expansion 2Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XVI: DB-1303/BNT323 Dose Expansion 14Experimental Treatment1 Intervention
China Only:Subjects who were previously treated with trastuzumab and taxane will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XVII: DB-1303/BNT323 Dose Expansion 13Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XVIII: DB-1303/BNT323 Dose Expansion 12Experimental Treatment2 Interventions
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 in combination with Pertuzumab on Day 1 of each cycle Q3W
Group XIX: DB-1303/BNT323 Dose Expansion 11Experimental Treatment1 Intervention
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
Group XX: DB-1303/BNT323 Dose Expansion 10Experimental Treatment3 Interventions
Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W along with ritonavir or itraconazole to assess the DDI potential
Group XXI: DB-1303/BNT323 Dose Expansion 1Experimental Treatment1 Intervention
Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 Day 1 of each cycle Q3W
DB-1303 is already approved in United States for the following indications:
🇺🇸 Approved in United States as BNT323/DB-1303 for:
- Advanced endometrial cancer (Breakthrough Therapy designation)
Find a clinic near you
Research locations nearbySelect from list below to view details:
D&H Cancer Research Center LLCMargate, FL
Laura & Isaac Perlmutter Cancer Center at NYC Langone HealthNew York, NY
Kerlo ResearchPhiladelphia, PA
Kerlo ResearchBala Cynwyd, PA
More Trial Locations
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Who is running the clinical trial?
DualityBio Inc.Lead Sponsor
BioNTech SEIndustry Sponsor
References
Docetaxel-cisplatin combination (DC) chemotherapy in patients with anthracycline-resistant advanced breast cancer. [2020]The safety and efficacy of a docetaxel-cisplatin combination (DC) were evaluated in 41 patients pretreated for advanced breast cancer (ABC).
Does neoadjuvant bevacizumab increase surgical complications in breast surgery? [2021]Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (bev) in the neoadjuvant setting. We sought to explore the safety of neoadjuvant cisplatin/bev in a protocol for triple negative breast cancer (TNBC).
Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133(high) cancer stem cells in vitro and in vivo. [2020]CD133 is a common marker of cancer stem cells (CSCs). We generated an anti-CD3/anti-CD133 bispecific antibody (BsAb) and bound it to the cytokine-induced killer (CIK) cells as effector cells (BsAb-CIK) to target CD133(high) CSCs. The killing of CD133(high) pancreatic (SW1990) and hepatic (Hep3B) cancer cells by the BsAb-CIK cells was significantly (p
Immunotoxin targeting CD133(+) breast carcinoma cells. [2022]CD133 expression enriches for tumor-initiating cells and is a negative prognostic factor in numerous cancers. We previously developed an immunotoxin against CD133 by fusing a gene fragment encoding the scFv portion of an anti-CD133 antibody to a gene fragment encoding deimmunized PE38KDEL. The resulting fusion protein, dCD133KDEL, demonstrated potent antitumor activity following intratumoral delivery into head neck cell carcinoma xenografts. However, the efficacy against other tumors and the tolerability of systemic administration remained unclear. The purpose of this study was to evaluate the tolerability and efficacy of dCD133KDEL in a systemic human breast carcinoma model. Time course viability studies showed that dCD133KDEL selectively inhibited MDA-MB-231 ductal breast carcinoma cells that contained a minority CD133(+) subpopulation, implicating CD133(+) cells as a source for self-renewal within this cell line. Furthermore, systemic administration of dCD133KDEL caused regression or inhibition of tumor growth in mice bearing an intrasplenic MDA-MB-231 tumor challenge as a model for metastatic disease. In the same model, combined therapy with dCD133KDEL and another immunotoxin designed to target the bulk tumor mass was the most effective therapy, supporting the idea that such combination therapies might better address tumor heterogeneity. dCD133KDEL shows promise as a therapeutic agent and as a biologic tool to study cancer stem cells.
Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T-cell-Engaging Antibody and CD8 T Cells. [2016]Cancer stem cells (CSC) drive tumorigenesis and contribute to genotoxic therapy resistance, diffuse infiltrative invasion, and immunosuppression, which are key factors for the incurability of glioblastoma multiforme (GBM). The AC133 epitope of CD133 is an important CSC marker for GBM and other tumor entities. Here, we report the development and preclinical evaluation of a recombinant AC133×CD3 bispecific antibody (bsAb) that redirects human polyclonal T cells to AC133(+) GBM stem cells (GBM-SC), inducing their strong targeted lysis. This novel bsAb prevented the outgrowth of AC133-positive subcutaneous GBM xenografts. Moreover, upon intracerebral infusion along with the local application of human CD8(+) T cells, it exhibited potent activity in prophylactic and treatment models of orthotopic GBM-SC-derived invasive brain tumors. In contrast, normal hematopoietic stem cells, some of which are AC133-positive, were virtually unaffected at bsAb concentrations effective against GBM-SCs and retained their colony-forming abilities. In conclusion, our data demonstrate the high activity of this new bsAb against patient-derived AC133-positive GBM-SCs in models of local therapy of highly invasive GBM.
Neoadjuvant anti-programmed Death-1 immunotherapy by Pembrolizumab in resectable nodal positive stage II/IIIa non-small-cell lung cancer (NSCLC): the NEOMUN trial. [2020]Immunotherapies targeting the PD1/PD-L1 pathway have had a large impact on the treatment of advanced NSCLC. Concerning multimodality tumor therapy, only few trials until today have been performed investigating neoadjuvant treatment with anti PD-1 immunotherapy prior to curative intent surgery. Aim of the NEOMUN investigator initiated trial (EudraCT-Number: 2017-000105-20; ClinicalTrials.gov Identifier: NCT03197467) is to assess feasibility and safety of pre-surgical anti PD-1 treatment in order to improve long term survival.
CD133 in Breast Cancer Cells: More than a Stem Cell Marker. [2020]Initially correlated with hematopoietic precursors, the surface expression of CD133 was also found in epithelial and nonepithelial cells from adult tissues in which it has been associated with a number of biological events. CD133 is expressed in solid tumors as well, including breast cancer, in which most of the studies have been focused on its use as a surface marker for the detection of cells with stem-like properties (i.e., cancer stem cells (CSCs)). Differently with other solid tumors, very limited and in part controversial are the information about the significance of CD133 in breast cancer, the most common malignancy among women in industrialized countries. In this review, we summarize the latest findings about the implication of CD133 in breast tumors, highlighting its role in tumor cells with a triple negative phenotype in which it directly regulates the expression of proteins involved in metastasis and drug resistance. We provide updates about the prognostic role of CD133, underlining its value as an indicator of increased malignancy of both noninvasive and invasive breast tumor cells. The molecular mechanisms at the basis of the regulation of CD133 levels in breast tumors have also been reviewed, highlighting experimental strategies capable to restrain its level that could be taken into account to reduce malignancy and/or to prevent the progression of breast tumors.
Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III NSCLC: Results of KINDLE, a Multicountry Observational Study. [2021]Stage III NSCLC is a heterogeneous disease requiring a multimodal management approach. We conducted a real-world, global study to characterize patients, treatment patterns, and their associated clinical outcomes for stage III NSCLC.
Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Stage III Non-Small-Cell Lung Cancer (PACIFIC). [2022]The PACIFIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS (the primary endpoints) vs. placebo in patients with unresectable, stage III NSCLC whose disease had not progressed after platinum-based, concurrent chemoradiotherapy (CRT). We report exploratory analyses of outcomes from PACIFIC by age.
Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer. [2021]Therapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).
A Pilot Study of Durvalumab (MEDI4736) with Tremelimumab in Combination with Image-Guided Stereotactic Body Radiotherapy in the Treatment of Metastatic Anaplastic Thyroid Cancer. [2023]Background: Metastatic anaplastic thyroid cancer (ATC) has a poor prognosis. This pilot study aims to evaluate tremelimumab plus durvalumab with stereotactic body radiotherapy (SBRT) to improve overall survival (OS). Methods: Eligible patients received up to 4 doses tremelimumab (75 mg) given q4 weeks and up to 1 year of durvalumab (1500 mg) given q4 weeks. SBRT at 9 Gy × 3 fractions was given within the first 2 weeks of the start of treatment. Paired biopsies (pretreatment and between 3 and 10 weeks after the first dose of the drug treatment) were done in the medically qualified patients. Major inclusion criteria are metastatic ATC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, no prior immunotherapy, and last anticancer treatment >7 days before starting the study. The primary endpoint was 1 year OS with the combination of durvalumab, tremelimumab, and SBRT in metastatic ATC patients with a target of 1 year OS in ≥2 out of 12 patients. Results: A total of 13 patients signed consent but only 12 patients ultimately participated in this trial. One patient who consented to the protocol became ineligible for this study due to continued decline in performance status. Patient characteristics were as follows: male (n = 6) with a median age of 71 years (range: 49-82), and ECOG = 1. Nine patients had prior neck radiation and nine patients had prior chemotherapy. Next-generation sequencing and PD-L1 staining were done in the nine patients where tissue was available. High microsatellite instability (MSI) corresponding to mismatch repair defect was noted in two patients. There were zero confirmed responses and only one patient had stable disease and was treated with ≥4 cycles of study drugs. The median time that the patients were under treatment was 11 weeks (1-28 weeks). MSI status did not affect treatment response. High MSI patients were on treatment for 8-14 weeks before disease progression. The median OS was 14.5 weeks with only 1 patient alive beyond 1 year. The presence of a BRAF or p53 mutation did not appear to affect treatment outcome. Conclusions: Tremelimumab and durvalumab with SBRT did not improve OS for ATC. Future research is needed to examine other novel immunotherapy combinations with or without radiotherapy in the treatment of ATC. Clinical Trial Registration: NCT03122496.
Treatment Characteristics and Real-World Progression-Free Survival in Patients With Unresectable Stage III NSCLC Who Received Durvalumab After Chemoradiotherapy: Findings From the PACIFIC-R Study. [2023]The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS).
Immunotherapy in triple negative breast cancer: beyond checkpoint inhibitors. [2023]The development of immunotherapy agents has revolutionized the field of oncology. The only FDA-approved immunotherapeutic approach in breast cancer consists of immune checkpoint inhibitors, yet several novel immune-modulatory strategies are being actively studied and appear promising. Innovative immunotherapeutic strategies are urgently needed in triple negative breast cancer (TNBC), a subtype of breast cancer known for its poor prognosis and its resistance to conventional treatments. TNBC is more primed to respond to immunotherapy given the presence of more tumor infiltrating lymphocytes, higher PD-L1 expression, and higher tumor mutation burden relative to the other breast cancer subtypes, and therefore, immuno-oncology represents a key area of promise for TNBC research. The aim of this review is to highlight current data and ongoing efforts to establish the safety and efficacy of immunotherapeutic approaches beyond checkpoint inhibitors in TNBC.
Bispecific Antibodies: A Novel Approach for the Treatment of Solid Tumors. [2022]Advancement in sequencing technologies allows for the identification of molecular pathways involved in tumor progression and treatment resistance. Implementation of novel agents targeting these pathways, defined as targeted therapy, significantly improves the prognosis of cancer patients. Targeted therapy also includes the use of monoclonal antibodies (mAbs). These drugs recognize specific oncogenic proteins expressed in cancer cells. However, as with many other types of targeting agents, mAb-based therapy usually fails in the long-term control of cancer progression due to the development of resistance. In many cases, resistance is caused by the activation of alternative pathways involved in cancer progression and the development of immune evasion mechanisms. To overcome this off-target resistance, bispecific antibodies (bsAbs) were developed to simultaneously target differential oncogenic pathway components, tumor-associated antigens (TAA) and immune regulatory molecules. As a result, in the last few years, several bsAbs have been tested or are being tested in cancer patients. A few of them are currently approved for the treatment of some hematologic malignancies but no bsAbs are approved in solid tumors. In this review, we will provide an overview of the state-of-the-art of bsAbs for the treatment of solid malignancies outlining their classification, design, main technologies utilized for production, mechanisms of action, updated clinical evidence and potential limitations.
Update on Classic and Novel Approaches in Metastatic Triple-Negative Breast Cancer Treatment: A Comprehensive Review. [2023]Triple-negative breast cancer (TNBC) accounts for almost 15% of all diagnosed breast cancers and often presents high rates of relapses and metastases, with generally poor prognosis despite multiple lines of treatment. Immunotherapy has radically changed the approach of clinicians towards TNBC in the last two to three years, even if targeted and specific therapeutic options are still missing; this unmet need is further justified by the extreme molecular and clinical heterogeneity of this subtype of breast cancer and by the weak response to both single-agent and combined therapies. In March 2023, the National Comprehensive Cancer Network (NCCN), the main association of cancer centers in the United States, released the last clinical practice guidelines, with an update on classic and novel approaches in the field of breast cancer. The purpose of this comprehensive review is to summarize the latest findings in the setting of metastatic TNBC treatment, focusing on each category of drugs approved by the Food and Drug Administration (FDA) and included in the NCCN guidelines. We also introduce part of the latest published studies, which have reported new and promising molecules able to specifically target some of the biomarkers involved in TNBC pathogenesis. We searched the PubMed and Scopus databases for free full texts reported in the literature of the last 5 years, using the words "triple-negative breast cancer" or "TNBC" or "basal-like". The articles were analyzed by the authors independently and double-blindly, and a total of 114 articles were included in the review.