Cancer, Solid Tumor
Conditions
Keywords
DXP-106, solid tumor, cancer, phase I
Brief summary
The goal of this clinical trial is to evaluate the safety and tolerability of DXP-106 in Chinese patients with advanced solid tumors. The main questions it aims to answer are: For Part I: 1. The safety and tolerability of DXP-106 monotherapy in patients with advanced solid tumors; 2. The dose-limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D); 3. The pharmacokinetics (PK) profile, the immunogenicity of DXP-106 following administration in patients with advanced solid tumors; 4. The preliminary efficacy of DXP-106 in patients with advanced solid tumors; 5. The pharmacodynamic (PD) profiles of DXP-106 following administration in patients with advanced solid tumors as exploratory objective; For Part2: 1. The safety and tolerability of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors; 2. The recommended dose of DXP-106 in combination with standard of care chemotherapy and/or potential responsive tumor types; 3. The efficacy of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors; 4. The PK profile and immunogenicity of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors; 5. The PD profiles of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors. The dose escalation is designed with five cohorts, including Cohort 1 (1.0 mg/kg), Cohort 2 (2.0 mg/kg), Cohort 3 (4.0 mg/kg), Cohort 4 (6.0 mg/kg), and Cohort 5 (8.0 mg/kg) in part 1. Each treatment cycle consists of 4 weeks, with administration once weekly (QW) in the first cycle and once every two weeks (Q2W) in subsequent cycles. Treatment will continue until disease progression, unacceptable toxicity, death, loss to follow-up, withdrawal of consent, or discontinuation due to other reasons. Based on the continuously obtained data from Part 1 monotherapy dose escalation, the Part 2 combination therapy exploration will be scheduled to commence. The combination therapy dose-escalation is planned to include three dose levels, tentatively designated as Dose Level 1 (DL1), DL2, and DL3 in PDAC patients. Dose escalation will follow the "traditional 3+3" rule, proceeding sequentially from DL1 to DL3. Safety Review Committee (SRC) will determine whether to proceed with escalation to higher doses based on available data, including but not limited to safety, tolerability, PK/PD, and preliminary efficacy. The SRC will discuss and make appropriate decisions when any other unanticipated circumstances occur during the clinical trial.
Detailed description
To accurately assess DLT, DLT-evaluable subjects are defined as one who meets any of the following criteria during the DLT evaluation period: 1. The patient experiences a DLT at any time after DXP-106 infusion during the DLT observation period. 2. The patient completes at least 75% of the planned total dose of DXP-106 infusion during the DLT evaluation period and have fulfilled the safety evaluation requirements during the DLT observation period. For Part 1 (monotherapy dose escalation) and Part 2 (combination therapy dose escalation) of this study, patients who discontinue prior to completion of the DLT evaluation period in the first cycle after the first dose for reasons other than DLT, or who do not meet any of the above criteria, will be considered non-evaluable for DLT. Subjects who are not evaluable for DLT due to non-DLT reasons will be replaced, leading to an increase in the actual sample size.
Interventions
DRUGDXP-106
DXP-106 as monotherapy or in combination with standard of care chemotherapy
Sponsors
Singlomics Biopharmaceuticals Zhuhai Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants who fully understand the trial objectives, nature, procedures, and potential adverse reactions, and who voluntarily agree to participate in the study and provide signed informed consent. * Patients aged 18 to 80 years (inclusive, based on the date of signing the informed consent form), both male and female. * Measurable disease as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST criteria within 4 weeks prior to screening. * Study Population * Part 1: Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who are ineligible for surgery or curative radiotherapy and have experienced disease progression after standard treatment or are intolerant to such therapy. Target tumor types include but are not limited to colorectal cancer, pancreatic ductal adenocarcinoma (PDAC), head and neck squamous cell carcinoma, lung cancer (LC), Ewing sarcoma (ES), and triple-negative breast cancer (TNBC). * Part 2: If the participant received adjuvant/neoadjuvant therapy before or after completing prior curative treatment, and the participant's disease has recurred, the interval between the end of adjuvant/neoadjuvant therapy and the first dose in this study must exceed 6 months. * LC patients: Patients with locally advanced/metastatic lung cancer confirmed by histology or cytology, who relapsed after first-line treatment and must meet the criteria for receiving platinum-based chemotherapy as first-line or second-line standard treatment; * PDAC Patients: Patients with newly diagnosed histologically or cytologically confirmed, unresectable or radiotherapeutically ineligible locally advanced or metastatic PDAC, who have not received previous treatment and are eligible for standard of care chemotherapy regimens. * ES patients: Patients with pathologically confirmed unresectable or locally advanced or metastatic Ewing's sarcoma that has failed standard treatment, and a detailed pathological report must be provided. Patients have received at least 1 but no more than 2 lines of systemic therapy previously, and must be eligible for standard chemotherapy regimens. * TNBC patients (for patients with bilateral breast cancer, both sides must be TNBC): Patients with histologically or cytologically confirmed, inoperable locally advanced or metastatic breast cancer, with ER, PR, and HER-2 all negative. The definition of ER and PR negativity is: IHC ER \< 1%, IHC PR \< 1%. The definition of HER-2 negativity is: IHC HER-2 (-) or (1+); for those with HER-2 (2+), FISH testing must be performed and the result must be negative. Patients must be eligible for standard chemotherapy regimens; * Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1. * Life expectancy \> 3 months. * Adequate organ function meeting the following criteria: * Hematology (without transfusion, hematopoietic growth factors, or medication to correct blood cell counts within 14 days prior to first dose): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 75 × 109/L (part1) or platelet count ≥ 100 × 109/L (part2), hemoglobin ≥ 9.0 g/dL. * Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) (for patients not receiving anticoagulant therapy); patients on oral anticoagulants with an INR between 2 and 3 were eligible. * Hepatic function: Total bilirubin (TBIL) ≤ 1.5 × ULN ); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; ALT and AST≤ 5.0 × ULN for patients with primary hepatocellular carcinoma (HCC) or hepatic metastases. * Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance \> 50 mL/min (calculated using the Cockcroft-Gault formula). * Both female and male patients of reproductive potential must have agreed to use reliable contraceptive methods during the trial and for 6 months after the last dose.
Exclusion criteria
* Participants with a history of hypersensitivity, particularly those allergic to the investigational drug or its excipients, or those who have previously experienced severe allergic reactions to macromolecular protein preparations/monoclonal antibodies. * Participants who have received live/live attenuated vaccines, etanercept or other TNF-α inhibitors, or any other investigational drug during or prior to participation in this study (within 4 weeks before the first dose of the investigational drug or within 5 half-life of the investigational drug, whichever is longer). * In Part 2, LC patients have received other anti-tumor drug treatments in addition to first-line treatment medications; patients with gene mutations that can be used as targets for targeted therapy (including but not limited to EGFR, ALK, ROS, KRAS) (excluding patients who have progressed on standard targeted therapy and whose next-line standard treatment is a platinum-based dual-drug regimen). * The toxicity from previous treatments has not alleviated to the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities (DLTs) within the first cycle of administraton of DXP-106 | From the first administration of DXP-106 on Cycle1Day1, including priming dose if any to the end of cycle1, assessed 4 weeks following C1D1 administration. | The severity of adverse events will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 6.0 (United States). A DLT is defined as any of the following adverse events occurring during the first cycle (starting from the first intravenous infusion of DXP-106, including priming dose if any) in either Part 1 (monotherapy dose escalation) or Part 2 (combination therapy dose escalation), including but not limited to: hematologic Toxicity; hepatic toxicity; other Grade ≥3 non-Hematologic toxicity; delays in subsequent treatment cycles exceeding 14 days due to persistent toxicity; any death clearly unrelated to the underlying disease or external causes. |
| Adverse events(AE) and serious adverse events(SAE) | From first administration of DXP-106 to safety follow up completion, assessed up to 13 months. | It will be assessed by the frequency, severity and nature of AEs, serious adverse event (SAE), changes in vital signs, physical examination, 12-lead ECG, infusion-related reactions and laboratory tests (haematology, serum chemistry, and urine), etc. The severity of AEs will be graded by the NCI CTCAE version 6.0 and the AE terms will be coded by the current version of the Medical Dictionary for Regulatory Activities (MedDRA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exposure levels of DXP-106 when administered in participants (Pharmacokinetics) | From the first administration of DXP-106, including priming dose if any, to the end of treatment, assessed up to 12 months. | PK collected from all participants receiving DXP-106 within 1 hour before the start of infusion, immediately after the end of infusion, 6 hours after priming dose if any; within 1 hour before the start of infusion on Cycle1Day1 and Cycle2Day1, immediately after the end of infusion, 3 hours, 6 hours, 24 hours (Cycle1Day2 and Cycle2Day2) and 48 hours (Cycle1Day3 and Cycle2Day3) after the start of infusion ; 168 hours (within 1 hour before infusion on Cycle1Day8 and Cycle2Day8); immediately after the end of infusion on Cycle1Day8; within 1 hour before the start of infusion, immediately after the end of infusion on Cycle1Day15, Cycle1Day22, Cycle2Day15, each administration in Cycle 3 and 4; within 1 hour before administration on cycle 6 and every 4 cycles beyond and end of treatment visit. |
| Anti-drug antibodies (ADAs) against DXP-106 (Immunogenicity) | From the first administration of DXP-106, including priming dose if any, to the end of treatment, assessed up to 12 months. | Blood samples will be collected from all participants in this study at the following time points to detect ADA and neutralizing antibodies (Nab, if applicable) for immunogenicity evaluation. The blood time points include: within 1 hour prior to infusion on priming dose if any, Cycle1Day1, Cycle1Day15, Cycle1Day22 (only for Part 1 monotherapy escalation and Part 2 PDAC patients; 4-week cycle); within 1 hour prior to each infusion in Cycle 2; within 1 hour prior to infusion on Cycle6 Day1and beyond, D1 (every 4 cycles ± 1 cycle) and at the end of treatment (EOT). The timing of immunogenicity blood sample collection may be appropriately adjusted based on accumulating human immunogenicity data. |
| Objective response rate (ORR and iORR) | From date of first administration until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months. | Tumor response is assessed according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 and iRECIST as per investigators' assessment. ORR/iORR is defined the proportion of patients who receive at least one dose of treatment and have measurable disease and is assessed as complete response (CR/iCR) or partial response (PR/iPR) during study treatment. ORR/iORR = (Number of patients achieving CR/iCR + Number of patients achieving PR/iPR) / Total number of efficacy-evaluable patients × 100% |
| Disease Control Rate (DCR and iDCR) | From date of first administration until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months. | DCR is defined as the proportion of patients who is assessed as CR/iCR, PR/iPR, or stable disease (SD/iSD), where SD/iSD must be maintained for at least 6 weeks from the first documentation. DCR/iDCR = (CR/iCR + PR/iPR + SD/iSD \[≥6 weeks\]) / total number of evaluable patients for efficacy × 100%; |
| Overall Survival (OS) | survival follow-up will be conducted once every 12 weeks (±4 weeks) after end of treatment visit until death, withdrawal of informed consent, loss to follow-up, or the data cutoff date, whichever comes first. assessed up to 12 months. | OS is defined as the time from the date of treatment to the date of death from any cause. |
| Progression-Free Survival (PFS) and iPFS | From date of first administration until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months. | PFS according to RECIST v1.1 and iRECIST as per the investigator's assessment. PFS is defined as the time from the date of treatment to the date of progressive disease (PD) or death from any cause, whichever occurs first. iPFS is defined as the time from the date of treatment to unconfirmed progressive disease (iUPD) or death from any cause, whichever occurs first, assessed per iRECIST v1.1 criteria. The event date for iPFS calculation shall be the date when progression criteria are first met (i.e., the date of iUPD), provided that iCPD (immune confirmed progressive disease) is confirmed at a subsequent assessment. If an assessment shows iUPD but subsequent assessment demonstrates iSD, iPR or iCR, this iUPD date shall NOT be used as the progression event date. If disease progression is not confirmed and no subsequent iSD, iPR or iCR is observed at later assessments, the date of the first iUPD shall still be used as the date meeting progression. |
| Duration of Response (DoR) and iDOR | From date of first administration until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months. | DoR assessed according to RECIST v1.1 and iRECIST, is defined as the time from the date of first documentation of overall response (CR/iCR or PR/iPR) to the date of first documented progressive disease (PD) or iUPD, or death from any cause, whichever occurs first. Calculated only for patients whose best overall efficacy is CR/iCR or PR/iPR. |
Countries
China
Contacts
CONTACTMingli Guo ML Guo, Master
CONTACTHuilian HL Zeng, Bachlor
Outcome results
None listed