Rare Malignant Neoplasm, Advanced Solid Tumors, Metastatic Solid Tumors
Conditions
Keywords
Rare Tumors, Platform Trial, Precision Medicine, Immunotherapy, Targeted Therapy, Cell and gene therapy, Tumor vaccine, Protein drug, Oncolytic virus
Brief summary
The goal of this Phase I/II observational and interventional platform study is to evaluate the safety and efficacy of multiple types of innovative anti-tumor drugs and new technologies in patients with rare solid tumors. The study utilizes multi-dimensional precision screening (including WES, RNAseq, mIHC, and quantitative proteomics) to match patients with specific sub-protocols. Key questions it aims to answer: Assess the safety of innovative therapies in rare tumor populations. Evaluate the objective response rate (ORR) and other efficacy metrics. Explore biomarkers related to therapeutic efficacy. Participants: Patients with metastatic or advanced rare solid tumors who have failed standard therapy or have no standard treatment options.
Detailed description
This is an open-label, non-randomized, multi-arm, single-center Phase I/II platform study (PLATFORM2). Based on the definition of rare tumors in China (incidence \< 2.5/100,000 or specific list), eligible patients will undergo multi-omics screening. Based on the molecular profiling results (gene variations or protein expression), patients will be assigned to corresponding treatment arms (Sub-studies). Therapies include small molecules, protein drugs, Cell and Gene Therapy (CGT) products, and therapeutic vaccines. The study employs a Clopper-Pearson Two-Stage Minimax design for each arm.
Interventions
BL-B01D1 is a first-in-class novel ADC consisting of an EGFRxHER3 bispecific antibody linked to a novel TOP-I inhibitor payload via a cleavable linker.
VSV injection uses a genetically engineered vesicular stomatitis virus (designated OVV-00) with enhanced safety and oncolytic activity as a vector platform, leveraging tumor cells as biological factories to express and produce multiple different universal tumor antigens and various bispecific or multispecific antibodies.
CVL006, a novel bispecific antibody, by fusing an anti-PD-L1 VHH domain with a humanized IgG1 anti-VEGF monoclonal antibody
IDOV-SAFETM is third-generation poxvirus oncolytic virus product. The most common treatment-related adverse events of the first-generation virus were fever (63.0%, including 3.7% grade 3) and abdominal pain (51.9%, including 7.4% grade 3). No grade 4 TRAEs occurred, and there were no treatment-related drug discontinuations or deaths, demonstrating good safety.
KXV01 is a first-in-class, novel, individualized TCR-T cell therapy generated in vivo. It consists of a structurally modified, third-generation, self-inactivating lentiviral vector carrying patient-specific tumor-targeting TCR sequences.
MT027 is an allogeneic universal chimeric antigen receptor T-cell (UCAR-T) injection targeting B7-H3. It consists of genetically engineered T cells that specifically recognize and kill cancer cells expressing B7-H3 antigen.
QH101 is an allogeneic TCR-enhanced Vδ2 T cell therapy product. It enhances the recognition of BTN proteins by introducing a specific binding element on the cell surface, utilizing the inherent killing ability of Vδ2 T cells to improve the efficiency of tumor cell killing. Simultaneously, QH101 does not express co-stimulatory signaling domains or CD3ζ domains, avoiding exhaustion caused by over-activation and effectively enhancing the persistence of cells in vivo.
Meta10-TIL is a metabolically enhanced tumor-infiltrating lymphocyte product genetically modified to autonomously secrete IL-10, enhancing T-cell proliferation, persistence, and anti-tumor activity.
TAEST1901 is a TCR-T cell therapy targeting the HLA-A\*02:01/AFP antigen complex. It involves transducing patient-derived autologous T cells with a lentiviral vector encoding a high-affinity TCR gene.
TC-N201 is a genetically engineered TCR-T cell product that recognizes the HLA-A2-restricted NY-ESO-1 tumor antigen and secretes an anti-PD-1 single-chain variable fragment (scFv). It is designed to enhance antitumor immunity by combining TCR-mediated tumor cell killing with local blockade of the PD-1/PD-L1 immune checkpoint pathway within the tumor microenvironment.
NK510 is a first-in-class, base-edited allogeneic natural killer (NK) cell product derived from healthy donor PBMCs. It utilizes RNP-based base editing technology to knock out the TIGIT gene, an inhibitory receptor that binds to CD155 on tumor cells. By eliminating TIGIT-mediated suppression, NK510 enhances intrinsic NK cell antitumor activity and demonstrates improved efficacy against CD155-expressing solid tumors.
CE120 is an innovative tumor immunotherapy that utilizes platelet membranes to cloak nanoparticles loaded with the immune activator R848, enabling tumor-targeted delivery via the natural adhesion of platelets to tumor cells. Upon intratumoral injection, CE120 activates local and systemic antitumor immune responses, including the induction of immune memory, to inhibit tumor growth, prevent recurrence, and clear tumors.
GV20-0251 is a monoclonal antibody targeting the highly conserved immunomodulatory protein IGSF8; it blocks the interaction between IGSF8 and its receptors on NK and DC cells, thereby conferring a mechanistic advantage in reversing immune resistance.
LYC001 is a PEG2000-DSPE-stabilized high-affinity IL-2 complex that maintains IL-2 in a uniform bound state, preventing the release of free IL-2 after dilution in body fluids.
YSCH-01 is a replication-dual-regulated human adenovirus type 5 vector engineered to selectively replicate in tumor cells and deliver an optimized recombinant pseudo-interferon gene (L-IFN), enabling high-level intratumoral L-IFN expression and secretion; through simultaneous oncolytic viral replication and potent immune stimulation, YSCH-01 achieves a dual antitumor mechanism that directly kills cancer cells while activating robust antitumor immune responses with minimal toxicity to normal tissues.
BMD006 is an inhaled mRNA tumor-associated antigen dry powder vaccine targeting lung cancer and solid tumors with lung metastasis, classified as an off-the-shelf anti-tumor product.
CREPT-618 Injection is an investigational nucleic acid-based therapeutic drug developed by Heya (Beijing) Pharmaceutical Technology Co., Ltd. It represents a cutting-edge approach in pharmaceutical technology, falling under the category of small nucleic acid drugs, which are considered a third generation of therapeutics following small molecules and antibodies.
PRG2505 (developmental code: V001 Injection) is an investigational in vivo chimeric antigen receptor T-cell (CAR-T) therapy developed by Pregene Biotech. It represents a novel approach that aims to generate CAR-T cells directly inside the patient's body, bypassing the complex and time-consuming traditional ex vivomanufacturing process.
IBI363 is a novel therapeutic drug independently developed by Innovent Biologics (Suzhou) Co., Ltd. Its active ingredient is a PD-1/IL-2 bispecific fusion protein, which simultaneously possesses dual functions: blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway
YL-201 is an investigational antibody-drug conjugate (ADC) developed by MediLink Therapeutics that targets B7-H3 (CD276), an immune checkpoint protein overexpressed on various solid tumor cells.
Sponsors
Study design
Eligibility
Inclusion criteria
1. Subjects must meet all of the following inclusion criteria: 2. Male or female subjects aged ≥16 years at the time of signing the informed consent form. 3. Histologically or cytologically confirmed malignancy. 4. ECOG performance status of 0-2 and an expected survival of more than 12 weeks. 5. Presence of measurable or evaluable disease for efficacy assessment, as determined by the investigator according to the individualized criteria defined in each sub-protocol. 6. Provision of fresh tumor biopsy tissue is recommended, obtained within 12 weeks prior to the first administration of study treatment, consisting of three core needle biopsy specimens. The biopsy tissue must not have been exposed to any antitumor therapy, systemic anti-infective treatment, or vaccination after collection. Peripheral blood samples are also recommended for molecular profiling and enrollment screening. 7. Provision of archival formalin-fixed paraffin-embedded (FFPE) tumor tissue from the primary lesion or a metastatic lesion (excluding bone metastases and lesions previously treated with radiotherapy) obtained within the past 2 years is recommended. The required material includes 15-20 unstained slides (4-6 μm thickness), of which 5 slides should be adhesive-coated and baked. If the above requirements cannot be met, enrollment eligibility may be determined at the investigator's discretion. 8. If pleural or peritoneal effusion is present, samples must be collected for pathological cytological examination, and provision of at least 50 mL of effusion fluid is recommended, if available. 9. If a primary tumor biopsy specimen has been provided, and a metastatic lesion is amenable to biopsy (as judged by the investigator), tissue from the metastatic lesion should be collected for pathological examination, and fresh tissue specimens are recommended. 10. Upon disease progression, if conditions permit (as judged by the investigator), collection of fresh tumor tissue from the same biopsy site at enrollment and/or from previously sampled metastatic lesions is recommended. 11. Toxicities from prior therapies must have resolved to ≤ Grade 1 or returned to baseline, according to NCI-CTCAE version 5.0, except for alopecia. 12. A negative pregnancy test is required for women of childbearing potential. Women not of childbearing potential are defined as those who are postmenopausal for at least 1 year, or who have undergone surgical sterilization or hysterectomy. 13. All enrolled subjects, regardless of sex, must agree to use effective contraception throughout the treatment period and for 8 weeks after the last dose of study treatment. 14. Subjects must voluntarily participate, provide written informed consent, comply with the study treatment and visit schedule, and be able to cooperate with safety and efficacy assessments.
Exclusion criteria
Subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 2 years. | Assessed by BICR and Investigator per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 2 years. | Assessed by BICR and Investigator. |
| Duration of Response (DoR) | Up to approximately 2 years. | The time from the first documented objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the first documented disease progression (PD) or death from any cause, whichever occurs first. |
| Disease Control Rate (DCR) | Up to approximately 2 years. | The percentage of patients who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) as their best overall response. |
| Overall Survival (OS) | Up to 1 year post-treatment. | The time from a specified starting point (usually randomization or first dose) to death from any cause. |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | From enrollment up to 30 days after last dose. | Assessment of safety according to NCI CTCAE v5.0. Including Treatment-Emergent Adverse Events (TEAE) and Treatment-Related Adverse Events (TRAE). |