Phase I Amount
$1,053,136
Quadriga Biosciences' new small molecule therapeutic, QBS-72S, combines a DNA alkylating moiety with an amino acid analogue that leverages the L-Type Amino Acid Transporter 1 (LAT1) to achieve transport across the blood brain barrier (BBB) and selective accumulation in tumor cells. Results from preclinical studies suggest QBS-72S is likely effective against brain metastases (brain mets) resulting from multiple cancer types, including triple negative breast cancer (TNBC). Currently, treatment for brain mets in patients with TNBC is limited to surgical intervention or radiotherapy, and drug development has been unsuccessful due to the challenge of transporting effective agents across the BBB. In this Direct-to-Phase II SBIR, Quadriga proposes to conduct a Phase 2a proof-of-concept clinical trial in patients with brain mets resulting from TNBC to test the safety and efficacy of QBS-72S using a Simon's two-stage design. Data from this study is expected to inform the design of a pivotal Phase 3 trial. Aim. Evaluate the safety and efficacy of QBS-72S in TBNC patients with brain metastases. Up to 25 patients with TNBC and brain mets will be identified by physicians at Stanford University and its referral network based on contrast MRI of the brain. Participants will be treated with the maximum tolerated dose (MTD) of QBS-72S administered intravenously every four weeks for up to 2 years. Tumor growth will be assessed by MRI the day prior to each administration for the first four months and every other month thereafter. The primary endpoint is objective response rate (i.e., the percentage of patients with ⤠25% growth in tumor size, no change in tumor size, or reduction in tumor size) at 3 months. Secondary endpoints include overall survival, length of progression-free survival, response of systemic disease, adverse events, and changes in lab-assessed patient parameters. Milestones: Using a Simon's two-stage Minimax design, if two or more of the first 15 evaluable TNBC patients treated with QBS-72S achieve an objective tumor response , the study will enroll 10 additional patients. If six or more patients (out of 25 total) have an objective tumor response within 3 months after initiating therapy, we will meet with the FDA to discuss the design of a registration trial for patients with brain mets resulting from TNBC. Impact-Successful completion of these studies will establish the foundation for a subsequent Phase 3 clinical trial. If QBS-72S proves efficacious in treating brain mets in patients with TNBC, it would be the first chemotherapeutic agent available specifically for this population. Findings of efficacy would also support further exploration into using QBS-72S to treat patients with other brain metastatic cancers, including lung cancer and melanoma. In addition, since LAT1 is highly expressed on many other forms of aggressive cancer, QBS-72S may be suitable for treating both systemic cancers and CNS metastases, especially in diseases like TNBC where there are few therapeutic options.
Public Health Relevance Statement: PROJECT NARRATIVE This project will test the safety and efficacy of Quadriga's new small molecule drug, QBS72S, in a clinical trial of patients with triple-negative breast cancer (TNBC) with brain metastases (tumor cells that have spread to the brain). TNBC is the most aggressive subtype of breast cancer: almost half of all women with TNBC develop brain metastases, and those who do typically survive for only three to six months longer. If QBS-72S proves effective in treating brain metastatic TNBC patients, it will hold promise for treating patients with other brain metastatic cancers, including lung cancer and melanoma.
Project Terms: Affect; Alkylating Agents; Alkylators; Amino Acids; aminoacid; Biological Sciences; Biologic Sciences; Bioscience; Life Sciences; Blood - brain barrier anatomy; Blood-Brain Barrier; Hemato-Encephalic Barrier; bloodbrain barrier; Brain; Brain Nervous System; Encephalon; malignant breast neoplasm; Breast Cancer; malignant breast tumor; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Clinical Trials; Diagnosis; Disease; Disorder; DNA; Deoxyribonucleic Acid; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Foundations; Growth; Generalized Growth; Tissue Growth; ontogeny; Human; Modern Man; In Vitro; indexing; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; melanoma; Malignant Melanoma; Mus; Mice; Mice Mammals; Murine; Neoplasm Metastasis; Metastasis; Metastasize; Metastatic Lesion; Metastatic Mass; Metastatic Neoplasm; Metastatic Tumor; Secondary Neoplasm; Secondary Tumor; cancer metastasis; tumor cell metastasis; Nervous System Physiology; Neurologic function; Neurological function; nervous system function; Patients; Physicians; Quality of life; QOL; Radiation therapy; Radiotherapeutics; Radiotherapy; radiation treatment; radio-therapy; treatment with radiation; Safety; Universities; Woman; African American; Afro American; Afroamerican; Black Populations; black American; improved; Phase; Metastatic malignant neoplasm to brain; Brain Metastasis; Metastatic Neoplasm to the Brain; Metastatic Tumor to the Brain; brain micrometastasis; Malignant neoplasm of lung; Malignant Tumor of the Lung; Pulmonary Cancer; Pulmonary malignant Neoplasm; lung cancer; Progression-Free Survivals; analog; Funding; Metastatic Neoplasm to the Central Nervous System; CNS Metastasis; Central Nervous System Metastasis; Metastatic Neoplasm to the CNS; Metastatic Tumor to the CNS; Metastatic Tumor to the Central Nervous System; Phase III Clinical Trials; Phase 3 Clinical Trials; phase III protocol; Therapeutic; Normal Tissue; Normal tissue morphology; Metastatic Cancer; Metastatic Malignant Neoplasm; Disseminated Malignant Neoplasm; Intravenous; Systemic disease; Heterograft; Heterologous Transplantation; Xenograft; Xenotransplantation; xeno-transplant; xeno-transplantation; Xenograft procedure; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; Tumor Cell; neoplastic cell; tumor growth; Participant; chemotherapeutic agent; Maximal Tolerated Dose; Maximally Tolerated Dose; Maximum Tolerated Dose; Modeling; response; drug development; Adverse Experience; Adverse event; Early-Stage Clinical Trials; Phase 1 Clinical Trials; phase I protocol; Phase I Clinical Trials; Amino Acid Channel; Amino Acid Transport Systems; Amino Acid Transporter; small molecule; Length; Dose; Data; Enrollment; enroll; Evaluable Disease; Evaluable; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Xenograft Model; xenograft transplant model; xenotransplant model; Process; Development; developmental; preclinical study; pre-clinical study; triple-negative invasive breast carcinoma; TNBC; triple-negative breast cancer; design; designing; Population; cancer type; Network-based; commercialization; tumor; safety testing; young woman; adolescent woman; adolescent women; phase III trial; phase 3 trial; Breast Cancer Patient; Breast Tumor Patient; small molecule therapeutics; objective response rate; preservation; secondary endpoint; secondary end point; primary endpoint; primary end point
