YL202 for Cancer
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Must be taking: EGFR TKI
Must not be taking: Steroids, Immunosuppressants
Disqualifiers: Cardiovascular disease, Brain metastases, ILD, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called YL202 to see if it is safe for patients with certain types of advanced lung and breast cancers that haven't responded to other treatments. The drug aims to target specific changes in the cancer cells to stop or slow their growth.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) for prior anticancer treatments before starting the study drug. It's best to discuss your current medications with the study team to understand any necessary adjustments.
What makes the drug YL202 (BNT326) unique for cancer treatment?
YL202 (BNT326) is unique because it targets the Mcl-1 protein, which is often overexpressed in certain cancers and helps them resist other treatments. By focusing on Mcl-1, YL202 may overcome resistance seen with other therapies that target different Bcl-2 family proteins.
12345Eligibility Criteria
This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, or hormone receptor-positive and HER2-negative breast cancer. Participants must have progressed after standard treatments, be able to use effective contraception, and not participate in other clinical studies. Major surgery within the last 4 weeks or need for systemic steroids disqualifies them.Inclusion Criteria
Informed of the trial before the start of the trial and voluntarily sign their name and date on the informed consent form
I agree to use effective birth control and not donate eggs or sperm during and 6 months after the study.
My organs and bone marrow are working well.
+10 more
Exclusion Criteria
I haven't had any cancer other than non-melanoma skin cancer or in situ disease in the past 3 years.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
I have not had major surgery in the last 4 weeks and do not expect any during the study.
+20 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive YL202 intravenously in a dose escalation format to evaluate safety and tolerability
36 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-8 weeks
Participant Groups
YL202 is being tested in this phase 1 study on patients who have heavily treated NSCLC or breast cancer. The goal is to assess its safety and how well it's tolerated when given to individuals whose cancers are either locally advanced or have spread beyond their original site.
1Treatment groups
Experimental Treatment
Group I: YL202 Dose escalationExperimental Treatment1 Intervention
YL202 will be administrated intravenously (IV) per dose level in which the patients are assigned.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Summit Cancer CenterSpokane Valley, WA
BRCR GlobalPlantation, FL
The University of Texas MD Anderson Cancer CenterHouston, TX
Karmanos Cancer InstituteDetroit, MI
More Trial Locations
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Who Is Running the Clinical Trial?
MediLink Therapeutics (Suzhou) Co., Ltd.Lead Sponsor
BioNTech SEIndustry Sponsor
References
Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade. [2021]An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use antiapoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of antiapoptotic Bcl-2 family members in clinical breast cancer datasets revealed greater expression and more frequent gene amplification of MCL1 as compared with BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like. While Mcl-1 protein expression was elevated in estrogen receptor α (ERα)-positive and ERα-negative tumors as compared with normal breast, Mcl-1 staining was higher in ERα+ tumors. Targeted Mcl-1 blockade using RNAi increased caspase-mediated cell death in ERα+ breast cancer cells, resulting in sustained growth inhibition. In contrast, combined blockade of Bcl-2 and Bcl-xL only transiently induced apoptosis, as cells rapidly acclimated through Mcl-1 upregulation and enhanced Mcl-1 activity, as measured in situ using Mcl-1/Bim proximity ligation assays. Importantly, MCL1 gene expression levels correlated inversely with sensitivity to pharmacologic Bcl-2/Bcl-xL inhibition in luminal breast cancer cells, whereas no relationship was seen between the gene expression of BCL2 or BCL2L1 and sensitivity to Bcl-2/Bcl-xL inhibition. These results demonstrate that breast cancers rapidly deploy Mcl-1 to promote cell survival, particularly when challenged with blockade of other Bcl-2 family members, warranting the continued development of Mcl-1-selective inhibitors for targeted tumor cell killing.Implications: Mcl-1 levels predict breast cancer response to inhibitors targeting other Bcl-2 family members, and demonstrate the key role played by Mcl-1 in resistance to this drug class. Mol Cancer Res; 15(3); 259-68. ©2016 AACR.
Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer. [2021]The B-cell lymphoma/leukemia 2 protein (BCL-2) may help many types of cancers to evade cell death. However, identifying exactly where this is the case is a challenge. ABT-199 is a small molecule that selectively inhibits BCL-2, which is currently in clinical trials in lymphoid malignancies. While inhibiting BCL-2 by itself can cause cell death in hematopoietic tumors, single-agent activity is harder to observe in solid tumors. Combining ABT-199 with tamoxifen, the standard endocrine therapy for estrogen receptor-positive breast cancers, 85% of which have BCL-2 expression, represents a new strategy to prime cancer cells for apoptosis and elicit better cancer cell death responses.
Enhanced therapeutic efficacy by simultaneously targeting two genetic defects in tumors. [2021]Targeting tumor-specific gene abnormalities has become an attractive approach in developing therapeutics to treat cancer. Overexpression of Bcl2 and mutations of p53 represent two of the most common molecular defects in tumors. In the nucleus, p53 induces cell cycle arrest, while it interacts with Bcl2 outside of the nucleus to regulate signal pathways involved in apoptosis. To potentiate antitumor activity, we tested a "double target" approach to antitumor therapy by combining H101, a recombinant oncolytic adenovirus that targets the inactive p53 in tumors, with a small interfering RNA (siBCL2) that targets Bcl2. In cell culture, the combined treatment significantly enhanced apoptosis and cytotoxicity as compared with treatment with either H101 or siBCL2 alone. In animals carrying tumor xenographs, combined H101 and siBCL2 treatment significantly inhibited tumor growth and prolonged survival. At the end of the study, all animals in the combined therapy group survived and two of the five animals showed complete eradication of their tumors. Interestingly, siBCL2 treatment increased H101 viral replication in both treated cells and tumor tissues. Simultaneously targeting two tumor-specific gene abnormalities using an oncolytic adenovirus and siRNA potentiates total antitumor activity.
ABT-199: taking dead aim at BCL-2. [2021]ABT-199 is a new selective small molecule inhibitor of BCL-2 that appears to spare platelets while achieving potent antitumor activity. Assays that can predict the efficacy of ABT-199 in individual tumors will be critical in determining how best to incorporate this promising agent into the armamentarium of cancer therapies.
A Novel Combination Treatment Targeting BCL-XL and MCL1 for KRAS/BRAF-mutated and BCL2L1-amplified Colorectal Cancers. [2022]Colorectal cancer is the third most commonly diagnosed cancer in the world, and exhibits heterogeneous characteristics in terms of genomic alterations, expression signature, and drug responsiveness. Although there have been considerable efforts to classify this disease based on high-throughput sequencing techniques, targeted treatments for specific subgroups have been limited. KRAS and BRAF mutations are prevalent genetic alterations in colorectal cancers, and patients with mutations in either of these genes have a worse prognosis and are resistant to anti-EGFR treatments. In this study, we have found that a subgroup of colorectal cancers, defined by having either KRAS or BRAF (KRAS/BRAF) mutations and BCL2L1 (encoding BCL-XL) amplification, can be effectively targeted by simultaneous inhibition of BCL-XL (with ABT-263) and MCL1 (with YM-155). This combination treatment of ABT-263 and YM-155 was shown to have a synergistic effect in vitro as well as in in vivo patient-derived xenograft models. Our data suggest that combined inhibition of BCL-XL and MCL1 provides a promising treatment strategy for this genomically defined colorectal cancer subgroup. Mol Cancer Ther; 16(10); 2178-90. ©2017 AACR.