Clinical Research Directory

Dual-Target CAR-NK Cells for Advanced Breast Cancer HER2+ TNBC

This study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. After a tumor antigen assessment (HER2/ERBB2, MUC1, ROR1,TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.

FUSCC Refractory TNBC Platform Study (FUTURE2.0)

This is a Phase II, open-label, Single-center platform study research based on molecular subtypes to explore precision therapy in refractory triple-negative breast cancer.

Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early TNBC. INVINCIBLE-4-SAKK

About 10-20% of all individuals with breast cancer have a so-called triple-negative tumor (TNBC). This type of breast cancer has a particularly unfavorable course and a higher mortality rate compared to other forms of breast cancer. Research studies show that it is important for individuals with TNBC to achieve a so-called pathologic complete response (pCR) to treatment. In the phase II study SAKK 66/22, it is being investigated whether the administration of the drug INT230-6 before surgery for breast cancer can increase the rate of pCR in the tumor and affected lymph nodes. The tolerability of INT230-6 as well as other factors such as response to treatment and the possibility of breast-conserving surgery are also being examined.

Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

This phase II trial studies how well carboplatin and nab-paclitaxel before surgery work in treating patients with triple negative breast cancer that is inflammatory or has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as carboplatin and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Peritumoral and Periganglionic Infiltration of Levobupivacaine Prior to Conservative Surgery for Triple-negative Breast Cancer

Breast cancer is one of the most common cancers among women. One in eight women in France will develop breast cancer during their lifetime (Inca). In 2023, 61,214 new cases of breast cancer were diagnosed in France, and in 2018, 12,146 deaths were attributed to this disease (e-cancer). Triple-negative breast cancer is characterised by the absence of hormone receptors (progesterone and oestrogen) and the HER2 protein on the surface of its cells. It is the breast cancer with the highest risk of recurrence, with a progression-free survival rate of 62% at 2 years (Di Lisa et al, 2023). In vitro, local anaesthetics have been shown to have breast tumour cytotoxicity, according to Borgeat in 2012. Among the various local anaesthetics tested in vitro, levobupivacaine has been shown to have the highest breast tumour cytotoxicity, according to Zhi-Fu Wu in 2022. At doses below systemic toxicity thresholds and at concentrations routinely used, levobupivacaine induces greater apoptosis and reduces the metabolic activity of breast tumour cells to a greater extent than lidocaine. Levobupivacaine has an antitumour effect on MDA-MB-31 cells, according to Zhi-Fu Wu in 2022. MDA-MB-31 cells overexpress the voltage-gated sodium channel (VGSC). The VGSC is composed of different subunits, including the Nav1.5 α subunit, which can be inactivated by levobupivacaine. In breast cancer, VGSC is mainly overexpressed in metastatic cancers and in the triple-negative line. The Nav1.5 α subunit of VGSC plays a role in tumour cell growth and migration. In vitro, a decrease in MDA-MB-231 cell migration has been demonstrated with levobupivacaine. Inactivation of Nav1.5 α with a molecule other than levobupivacaine (e.g., phenytoin) has shown antitumour effects in vitro and in vivo (Chen et al, 2022). Targeting VGSC using a well-characterised local anaesthetic such as levobupivacaine could be a strategy for reducing the metastatic risk of triple-negative breast cancers, especially since surgical infiltration of local anaesthetics is a commonly performed procedure within the scope of their marketing authorisation. Badwe et al. (2023) demonstrated a benefit of peritumoral injection of 0.5% lidocaine on overall survival and progression-free survival in women with operable breast cancer. However, in this study, the type of surgery varied (lumpectomy or mastectomy) and only a peritumoral injection was performed (without periganglionic injection). Furthermore, no specific analysis of the triple-negative breast cancer subgroup was presented. Targeting VGSC using a well-characterised local anaesthetic such as levobupivacaine could be a strategy for reducing the metastatic risk of triple-negative breast cancers, especially since surgical infiltration of local anaesthetics is a procedure commonly performed within the scope of their marketing authorisation. Badwe et al. Furthermore, no specific analysis of the triple-negative breast cancer subgroup was presented. Thus, no high-level evidence (prospective, randomised, double-blind) studies have been conducted on the benefits of peritumoral and periganglionic levobupivacaine infiltration in the context of conservative surgery (lumpectomy) for triple-negative breast cancer. The literature only contains in vitro studies, retrospective studies and a few rare prospective studies that were not conducted blind

Prediction of Radiotherapy Efficacy in Patients With Triple-negative Breast Cancer

Recurrence of triple-negative breast cancer (TNBC) occurs in around 30% of patients within 3 years of treatment. For some TNBC patients, recurrence occurs on average 2.6 years after treatment, while for others recurrence does not occur early. TNBC patients can therefore be divided into two groups: those with early recurrence and those who respond well to treatment. At present, there are no biomarkers to differentiate these two groups. Some studies suggest that radiation-induced inflammatory cytokines may stimulate the development of new metastases. Gene expression profiling or protein signatures have not been able to define such biomarkers. The aim of this research protocol is to recruit patients to evaluate if the elevation of the cytokines IL-1β, IL-5 and IL-6 in plasma collected during radiotherapy can be used to predict TNBC patients at high risk of recurrence.

JS207 Combination Therapy in Triple-negative Breast Cancer

This is an open-label, multi-center, phase II clinical study to preliminarily evaluate the efficacy and safety of JS207 combined with 9MW2821 or albumin paclitaxel as first-line therapy in patients with recurrent or metastatic TNBC.

Nab-P+Cb+PD1 Inhibitors as Neoadjuvant Therapy for Early TNBC

We plan to explore the efficacy and safety of albumin-bound paclitaxel+carboplatin+Camrelizumab in neoadjuvant therapy for early TNBC patients, optimize the administration method and drug combination therapy.

Reverse Triple Negative Immune Resistant Breast Cancer

This is a Phase II, open-label, seven-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, theophylline) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.

Pembrolizumab and Chemotherapy Treatment or no Treatment Guided by the Level of TILs in Resected Early-stage TNBC

Triple-negative breast cancer (TNBC) is a group of tumors that occurs mainly in young, premenopausal women and accounts for 10-20% of breast cancers. Over the past decade, the incidence of women diagnosed with early-stage TNBC has significantly increased due to the widespread use of screening mammography. Treatment of patients with localized TNBC mainly involves surgery and (neo)adjuvant chemotherapy with or without radiotherapy. However, the benefit of chemotherapy may be controversial in patients with early-stage TNBC defined by small size and absence of lymph node involvement, and with significant tumor lymphocyte infiltration. The ETNA study is a phase II trial designed to evaluate a chemotherapy de-escalation strategy in patients with TNBC T1b/c N0M0 and stromal TILs (sTILs) ≥ 30%. ETNA comprises two cohorts defined according to the level of TILs and the age of patients. Patients aged \> 40 years with 30% ≤ sTILs \< 50% and those aged ≤ 40 years with 30% ≤ sTILs \< 75% will be included in the cohort 1 and will receive adjuvant pembrolizumab 200 mg every three weeks for 9 cycles and Paclitaxel 80 mg/m² weekly for 12 cycles. Patients aged \> 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75% will be included in cohort 2 and will not receive adjuvant treatment, they will undergo standard surveillance every six months.

Study of JANX008 in Subjects With Advanced or Metastatic Solid Tumor Malignancies

This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.

NeoAdjuvant Therapy Comparing Sacituzumab Govitecan+Pembrolizumab vs. SoC Chemotherapy in Clinical Stage II-III, Triple-negative Early Breast Cancer

TNBC is a heterogeneous disease with distinct pathological, genetic, and clinical features among subtypes. Treatment results for high-risk primary TNBC remain poor compared to other breast cancer subtypes. Preoperative chemotherapy is the standard of care for patients with stage II or III primary TNBC. Multiple lines of clinical evidence demonstrate that TNBC patients who achieve a pCR to NACT, (ypT0/is ypN0), have an excellent long-term prognosis. A meta-analysis of individual patient data confirmed a strong association of pCR after NACT with improved long-term event-free survival (EFS, hazard ratio \[HR\] 0.24) and overall survival (OS, HR 0.16) benefit. Taxane- and anthracycline-based neoadjuvant regimens generally result in pCR rates between 25-50% \[REFs\], whereas the addition of platinum increases pCR rates to approximately 50-55%. The KEYNOTE-522 trial has demonstrated that the addition of the immune-checkpoint inhibitor PEM to anthracycline- (AC), taxane- and platinum-based NACT resulted in a significant increase in pCR rates to nearly 65%, associated with a significant reduction of recurrences (EFS, HR 0.65 at 5 years) and improvement of OS (HR 0.66). Based on these results, the KEYNOTE-522 regimen has been approved by the FDA and EMA and has become the standard of care for patients with stage II or III TNBC. Despite this significant progress, two major questions remain unresolved which will be investigated in the ADAPT-TN-IV trial: 1. Do all patients require the full 6 months of NACT as per KEYNOTE-522 or is there a subgroup of patients who are sufficiently treated with 12 weeks of NACT plus PEM? 2. Can incorporation of ADCs into the KEYNOTE-522 regimen improve response and outcomes in patients without an optimal early response? The outcome of patients with residual disease after 24 weeks of NACT and PEM remains suboptimal and there is an urgent need for more effective strategies. ADCs such as SG have demonstrated superior efficacy compared to standard chemotherapy in metastatic TNBC, resulting in substantially higher response rates and improved progression-free (PFS) and OS. Combination studies of ADCs and immunotherapy in metastatic TNBC have demonstrated significant activity, suggesting possible synergistic activity It is therefore a logical next step to investigate, whether the incorporation of SG in the NACT regimen can improve pCR rates and EFS results in patients who have residual clinical disease after 12 weeks of NACT with CARBO/PAC + PEM.

Nab-paclitaxel Plus Carboplatin Versus Nab-paclitaxel Plus Epirubicin in the Neoadjuvant Therapy for Breast Cancer

This is a multicenter, open, randomized, comparison study. Triple-negative breast cancer (TNBC) is a term applied to breast cancer cases that have \<1% expression of the estrogen receptor (ER) and the progesterone receptor (PR) and do not over express HER2. Neoadjuvant therapy is often used to reduce the size of tumors, especially in locally advanced tumors. The purpose of this therapy is to make part of patients operable and to facilitate breast-conserving surgery. The purpose of this study is to assess the efficacy and safety of the following two proposals: nab-paclitaxel plus carboplatin versus nab-paclitaxel plus epirubicin, in order to provide support for rational clinical application. The total number of patients to be included in this study is 520 patients.

A Study on the Efficacy and Safety of Oral All-trans Retinoic Acid Combined With Toripalimab in TNBC.

To evaluate the clinical efficacy and safety of oral all-trans retinoic acid in combination with toripalimab in patients with locally advanced, recurrent, or metastatic triple-negative breast cancer who had failed second-line and subsequent therapy.

Diagnostic Efficacy and Dosimetry of MNPR-101-DFO*-89Zr in Patients With Solid Tumors

This is an open-label pilot study of a new PET/CT imaging agent MNPR-101-DFO\*-89Zr in patients with solid tumor cancers. These cancers may include bladder/urothelial, triple-negative breast, lung, colorectal, gastric, ovarian, and pancreatic cancers. MNPR-101-DFO\*-89Zr is made of MNPR-101, a humanized IgG1 monoclonal antibody and a radioisotope Zirconium-89. This imaging agent may show where tumors are present in the body using a PET-scan. Participants will be injected with the radioactive tracer once. After injection, participants will have 3 PET-scans. Each PET-scan will take about 30 minutes. The PET-scans are on separate days within 10 days after injection (e.g., 2 hours after injection, plus 3-5 days and 7-10 days after injection). Furthermore, the investigators will take blood samples 6 times (5 mL each). Blood pharmacokinetics (PK) will be measured on Day 1 at 10 min, 1h, 2h, once on Days 3-5, and once on Days 7-10. The study will see if the new imaging agent correctly shows all tumors. In the future, this method may be useful to help predict who will benefit from certain therapies.

Dose-Escalation of MNPR-101-PCTA-177Lu in Solid Tumors

This is an open-label, uncontrolled, multi-center, phase 1a MNPR-101-PCTA-177Lu dose-escalation study in patients with solid tumor cancers. Patients must have participated in the imaging study MNPR-101-D001 (actively recruiting, diagnostic study of MNPR-101-DFO\*-89Zr). * TITE-BOIN will be used to objectively determine dose increase, no dose change, or dose decrease for each group of two patients. * The treatment period consists of two 12-week cycles. Patients will receive three equal fractions of MNPR-101-PCTA-177Lu with radioactivity ranging from 480-2240 MBq on each of Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (12 weeks after Cycle 1 Day 1). * Patients will be followed for 12 weeks after their last dose of MNPR-101-PCTA-177Lu. * Patients will be imaged at specific timepoints during the study.

Cadonilimab Combined With Chemotherapy as First or Second Line Treatment in Recurrent or Metastatic Triple Negative Breast Cancer

The prognosis of recurrent and metastatic triple negative breast cancer (TNBC) is poor, and chemotherapy is still the main treatment for TNBC. Some studies have shown that combination therapy of antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) significantly improves clinical benefit over PD-1 antibody alone. However, broad application of this combination has been limited by toxicities. Cadonilimab is a humanized immunoglobulin G1 bispecific antibody targeting PD-1 and CTLA-4. It mutates to eliminate Fc receptor and complement-mediated cytotoxic effects. The purpose of this study is to evaluate the efficacy and safety of Cadonilimab combined with chemotherapy as a first or second-line treatment of recurrent and metastatic TNBC. This study is a multicenter, single arm, phase II, non randomized, open label, Simon two-stage design. It is planned to enroll 27 late stage TNBC patients.

A Study of BL-B01D1+PD-1 Monoclonal Antibody in Patients With Unresectable Locally Advanced or Recurrent Metastatic Triple-negative Breast Cancer

This phase II study is a clinical study to explore the efficacy and safety of BL-B01D1 combined with PD-1 monoclonal antibody in patients with unresectable locally advanced or recurrent metastatic triple-negative breast cancer.

INCMGA00012 and Pelareorep for the Treatment of Metastatic Triple Negative Breast Cancer, IRENE Study

This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012 and pelareorep and to see how well they work in treating patients with triple negative breast cancer that has spread to other parts of the body (metastatic). INCMGA00012 is a monoclonal antibody that works by attaching to the programmed cell death protein 1 (PD-1) and blocking this pathway, allowing the immune system to recognize and attack the cancer cells. Pelareorep is a type of virus called reovirus which occurs naturally and may break down cancer cells. Giving INCMGA00012 and pelareorep may slow the growth and spread of the cancer to another part of the body.

Carboplatin Intensified Chemotherapy for TRIple NEgative Breast Cancer(CITRINE)

This is a prospective, single center, randomized, open-labled stage III clinical trial comparing the efficacy and safety of anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel versus dose-dense anthracyclin followed by weekly paclitaxel combined with carboplatin for high-risk, triple-negative early breast cancer.

Albumin-Bound Paclitaxel Combined With Antiangiogenic Agents in First-line Treatment of Relapsed or Metastatic TNBC

This is a prospective, randomized, open-label clinical study. 128 patients with relapsed or metastatic triple-negative breast cancer (TNBC) who had not been systematically treated are going to be enrolled and randomly assigned to 3 groups. Group A: albumin-bound paclitaxel (260mg/m2, intravenous infusion, once every 3 weeks). Group B: albumin-bound paclitaxel (260mg/m2, intravenous infusion, once every 3 weeks)+ apatinib mesylate tablet (500 mg, orally, once daily, every 3 weeks). Group C: albumin-bound paclitaxel (260mg/m2, intravenous infusion, once every 3 weeks) + bevacizumab (7.5mg/kg, intravenous infusion, once every 3 weeks). The dosages of therapeutic drugs are allowed to be adjusted appropriately according to the toxic reaction of the patients. Patients in three groups continued to take medication until disease progression/death/toxicity was intolerable/the patient or investigator decided to discontinue the medication. The primary endpoint is progression-free survival (PFS). Secondary endpoints are objective response rate (ORR), clinical benefit rate (CBR, complete response (CR)+ partial response (PR) + stable disease (SD, \> 6 months)), overall survival (OS), adverse events (AE), and potential predictive biomarker parameters related to treatment response (VEGF-A expression level) in peripheral blood.

Non-Inferiority Study on MRNA-lncRNA Model in Low-Risk Triple-Negative Breast Cancer Patients

To compare the efficacy and safety of different adjuvant chemotherapy regimens for low-risk triple-negative breast cancer patients predicted by mRNA-lncRNA model

Tislelizumab Combined with Nab-Paclitaxel for First-Line Treatment of Advanced Triple-Negative Breast Cancer with Bone Metastasis，an Exploratory, Single-Arm, Multicenter Phase II Clinical Study

The goal of this clinical trial is to learn if Tislelizumab Combined with Nab-Paclitaxel works to treat patients of TNBC with bone metastasis as first line treatment. It will also learn about the safety of the combination. The main questions it aims to answer are: How effective is the combination therapy of tislelizumab and nab-paclitaxel in treating advanced first-line triple-negative breast cancer with bone metastasis? And is it safe? Participants will: * Receive the treatment as follows: Tislelizumab, 200mg, intravenous, every 3 weeks; nab-paclitaxel, 125mg/m2 on day 1 and day 8, followed by once every three weeks; RANKL inhibitor chosen by investigator is administered at a dose of 120 mg every 4 weeks, with dosing on Days 1, 8, and 15 during the first cycle. * Visit the clinic once every 3 weeks for checkups and tests * Keep a diary of their symptoms and the number of times they use a rescue inhaler

Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067

This is a multiphase, multicenter study, which includes a Phase 1a open-label, dose escalation monotherapy study of ST-067 given as an SC injection with or without obinutuzumab \[Gazyva®\] pre-treatment, by IV infusion, and in combination with pembrolizumab. A Phase 2 monotherapy arm is also planned; the exact design of the Phase 2 study elements with respect to formulation and pre-treatment will be determined after completion of the Phase 1 study portion of the trial.