Unresectable Locally Advanced or Metastatic Pancreatic CancerPhase 1/2NCT05832892
Surufatinib Combined With KN046 and AG Regimen Chemotherapy as First-Line Treatment for Unresectable Advanced Pancreatic Cancer
A Phase 1/2 study testing surufatinib, KN046 and gemcitabine in people with Unresectable Locally Advanced or Metastatic Pancreatic Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
Advanced pancreatic cancer is a highly aggressive and fatal disease with an extremely low 5-year survival rate. Combined chemotherapy is the mainstay of treatment for patients with unresectable advanced pancreatic cancer, and the combination of nab-paclitaxel and gemcitabine (AG regimen) has been one of the most… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Unresectable Locally Advanced or Metastatic Pancreatic Cancer
- What is being tested?
- surufatinib, KN046 and gemcitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2023to 1 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed content obtained prior to treatment.
- Male or female, age ≥ 18 years and ≤ 75 years.
- Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that originated from the pancreatic ductal epithelial, with image-documented unresectable locally advanced or distant metastatic disease.
- Patients have received no previous local treatment such as surgery, radiotherapy, ablation, or any systemic treatment for advanced/metastatic pancreatic cancer, including neoadjuvant and/or adjuvant therapy.
- Have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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- Expected overall survival of ≥ 6 months.
- Laboratory test results within 7 days prior to first dose of study drugs must meet the following criteria:
- absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L and hemoglobin (HGB) ≥ 90 g/L.
- total bilirubin (TBil) ≤ 1.5 × the upper limit of normal (ULN).
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN in the absence of liver metastases; ALT and AST ≤ 3 × ULN in the presence of liver metastases.
- serum creatinine (SCr) ≤ 1.5 × ULN and creatinine clearance (CCl) ≥ 50 mL/min (calculated according to the Cockcroft-Gault formula).
- urine protein <2+ in urine analysis; if urine protein ≥2+, 24-hour urine protein quantification should be <1g.
- international normalized ratio (INR) ≤ 1.5 and partial activation prothrombin time (APTT) ≤ 1.5 × ULN.
- Female subjects of childbearing age or male subjects whose partner is a female of childbearing age should use effective contraception from at least 1 month prior to the first dose of study drugs to 6 months after the last dose of study drugs.
Who cannot join
- Adverse events (AEs) due to previous anti-tumor therapy have not recovered to CTCAE Grade ≤1 (except for hair loss, skin pigment changes, or Grade ≤ 2 neurotoxicity).
- Other malignancies diagnosed within past 5 years (except basal cell carcinoma of the skin or squamous cell carcinoma and carcinoma in situ of the cervix that have been effectively controlled).
- Presence of central nervous system (CNS) metastases at screening, or have a history of CNS metastases.
- Patients who have received approved systemic anti-tumor therapy within 4 weeks before the first dose of study drugs, including chemotherapy, biological therapy, targeted therapy, hormone therapy, traditional Chinese medicine therapy (with clear anti-tumor indications in the label), etc.
- Patients who have received radical radiotherapy (including radiotherapy involving > 25% bone marrow) within 4 weeks prior to the first study drugs reception; Or brachytherapy (e.g., implanted radioparticles) within 60 days prior to the first dose of the study drugs; Or palliative radiotherapy for bone metastases within 1 week prior to first dose of the study drugs.
- Patients who have undergone major surgery within 4 weeks before receiving first dose of study drugs, or have unhealed wounds, ulcers or fractures.
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- Vaccination within 4 weeks before the first dose of study drugs or plan to have during the study period, except for inactivated vaccines.
- Patients who have previously received anti-VEGF/VEGFR agents and have experienced disease progression during treatment or within 3 months after the last dose.
- Patients with uncontrollable malignant pleural effusion, ascites, or pericardial effusion (no response to diuretics or puncture as per the investigator's judgement).
- Presence of gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding in unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator.
- Patients with evidence or history of thrombosis or significant bleeding tendency (bleeding >30 mL within 2 months, hematemesis, melena, hematochezia, or hemoptysis >5mL within 4 weeks) within 2 months prior to the first dose of the study drugs.
- Patients who have arterial thrombosis or deep vein thrombosis within 6 months, or have thromboembolic events (including stroke and/or transient ischaemic attack) within 12 months prior to first dose of the study drugs.
- Patients who are receiving anti-tuberculosis therapy for active pulmonary tuberculosis, or have had anti-tuberculosis therapy within 1 year prior to first dose of the study drugs.
- Patients with a previous or current history of pulmonary disorder that may interfere the identification and management of suspected drug-related pulmonary toxicity, including pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc. (radiation pneumonia in radiotherapy areas is allowed).
- Presence of corneal lesions, including but not limited to bullous keratopathy, shingle corneal degeneration, corneal abrasions, corneal ulcers, keratitis, etc.
- History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive; known Hepatitis C virus (HCV) infection with HCV RNA positive; or other hepatitis, liver cirrhosis, etc.
- Positive for human immunodeficiency virus (HIV) antibodies.
- Meet any of the following criteria for cardiac function:
- Clinically significant arrhythmias or conduction abnormalities requiring clinical intervention.
- Electrocardiogram (ECG) indicating an QT interval (QTcF) of > 480 msec.
- Clinically significant cardiovascular diseases, including acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris, coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification III/IV, ventricular arrhythmias needing drug intervention, LVEF <50%.
- Previous or current autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener syndrome, Graves' disease, rheumatoid arthritis, pituitary inflammation, ocular pigmentitis, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), with exceptions as follows: type I diabetes, hormone replacement therapy-stabilized hypothyroidism, psoriasis or vitiligo that does not require systemic therapy.
- Women who are pregnant or lactating.
- Known history of allergy to the relevant ingredients of the study drugs.
- Subjects who have received investigational treatments in other clinical studies within 4 weeks prior to first dose of study drugs.
- Patients who have any disorder or condition that may affect absorption of the study drugs, or who are unable to take oral medication.
- Patients unsuitable for participating due to other reasons as per investigator's determination.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital
Shanghai, Shanghai Municipality, 200000
Wen-Quan Wang, MD, PhD, +86 21 31587861, wang.wenquan@zs-hospital.sh.cn
About this study
Official title: A Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of Surufatinib in Combination With KN046 and AG Regimen Chemotherapy for the First-Line Treatment of Unresectable Advanced Pancreatic Cancer
Advanced pancreatic cancer is a highly aggressive and fatal disease with an extremely low 5-year survival rate. Combined chemotherapy is the mainstay of treatment for patients with unresectable advanced pancreatic cancer, and the combination of nab-paclitaxel and gemcitabine (AG regimen) has been one of the most commonly used regimens for more than a decade. However, chemo-resistance often occurs within half a year and the efficacy remains unsatisfied with an overall survival of only 9~11 months.
Immune checkpoint inhibitors (ICIs) such as anti-PD-1/L1 antibody and anti-CTLA-4 antibody have demonstrated encouraging anti-tumor efficacy in multiple solid tumors including lung cancer, gastric cancer, and esophageal cancer, while obtained controversial results when combined with chemotherapy in pancreatic cancer. Recently, the immune-suppression tumor microenvironment (TME) of pancreatic cancer has been described in several pre-clinical studies, which may explain the resistance against ICIs and chemotherapy.
Read more
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific antibody with innovative designs include a proprietary CTLA-4 domain antibody with a significantly improved safety profile, a bispecific antibody fused with PD-L1 antibody targeting the TME with high PD-L1 expression. Recent clinical studies have shown promising anti-tumor activity of KN046 in pancreatic cancer.
Surufatinib, also known as HMPL-012 or Sulfatinib, is a small molecular tyrosine kinase inhibitor (TKI) targeting the Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor (FGFR) and Colony Stimulating Factor-1 Receptor (CSF-1R), which has a dual mechanism of action of anti-angiogenesis and regulation of immune microenvironment. Previous studies have suggested synergic effect of surufatinib in combination with anti-PD-1 antibodies.
This phase Ib/II clinical trial is intended to investigate the activity and safety of the combination of surufatinib combined with KN046 and the AG regimen chemotherapy as first-line treatment in patients with unresectable locally advanced or metastatic pancreatic cancer.
Read the detailed description
Advanced pancreatic cancer is a highly aggressive and fatal disease with an extremely low 5-year survival rate. Combined chemotherapy is the mainstay of treatment for patients with unresectable advanced pancreatic cancer, and the combination of nab-paclitaxel and gemcitabine (AG regimen) has been one of the most commonly used regimens for more than a decade. However, chemo-resistance often occurs within half a year and the efficacy remains unsatisfied with an overall survival of only 9~11 months.
Immune checkpoint inhibitors (ICIs) such as anti-PD-1/L1 antibody and anti-CTLA-4 antibody have demonstrated encouraging anti-tumor efficacy in multiple solid tumors including lung cancer, gastric cancer, and esophageal cancer, while obtained controversial results when combined with chemotherapy in pancreatic cancer. Recently, the immune-suppression tumor microenvironment (TME) of pancreatic cancer has been described in several pre-clinical studies, which may explain the resistance against ICIs and chemotherapy.
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific antibody with innovative designs include a proprietary CTLA-4 domain antibody with a significantly improved safety profile, a bispecific antibody fused with PD-L1 antibody targeting the TME with high PD-L1 expression. Recent clinical studies have shown promising anti-tumor activity of KN046 in pancreatic cancer.
Surufatinib, also known as HMPL-012 or Sulfatinib, is a small molecular tyrosine kinase inhibitor (TKI) targeting the Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor (FGFR) and Colony Stimulating Factor-1 Receptor (CSF-1R), which has a dual mechanism of action of anti-angiogenesis and regulation of immune microenvironment. Previous studies have suggested synergic effect of surufatinib in combination with anti-PD-1 antibodies.
This phase Ib/II clinical trial is intended to investigate the activity and safety of the combination of surufatinib combined with KN046 and the AG regimen chemotherapy as first-line treatment in patients with unresectable locally advanced or metastatic pancreatic cancer.
- Being tested
- surufatinib, KN046, gemcitabine, Nab paclitaxel
- Keywords
- Pancreatic Cancer, Surufatinib, KN046, Nab-paclitaxel, Gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
surufatinibDrug
Also called HMPL-012, Sulfatinib
In phase Ib, surufatinib will be orally administrated 200 mg once a day (QD) or 250 mg QD per cohort escalation assignment on a 21-day cycle.
In phase II, surufatinib will be orally administrated at RP2D as determined in phase Ib.
KN046Drug
Nab-paclitaxel will be administrated at 125 mg/m2 intravenously on day 1 and 8 of each 21-day cycle.
gemcitabineDrug
Also called GEMZAR
Gemcitabine will be administrated at 1000 mg/m2 intravenously on day 1 and 8 of each 21-day cycle.
Nab paclitaxelDrug
Also called nanoparticle albumin-bound paclitaxel, Abraxane, ABI-007
Nab-paclitaxel will be administrated at 125 mg/m2 intravenously on day 1 and 8 of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| surufatinib + KN046 + nab-paclitaxel + gemcitabine | Experimental | In the phase Ib of dose escalation, all patients enrolled will receive: nab-paclitaxel at 125 mg/m2 on days 1 and 8, gemcitabine at 1000 mg/m2 on days 1 and 8, KN046 at 5 mg /kg on day 1, plus surufatinib per cohort escalation assignment starting with 200 mg. The combination treatment repeats every 3 weeks, until disease progression, death, intolerable toxicity, or withdrawal of informed consent. Dose-limiting toxicity will be evaluated 28 days after first dose to determine the recommended phase 2 dose (RP2D) of surufatinib.
Patients enrolled in the phase II of dose expansion will receive the combination regimen of nab-paclitaxel plus gemcitabine plus KN046 plus surufatinib as determined in the phase Ib. Receives: Drug: surufatinib; Drug: KN046; Drug: gemcitabine; Drug: Nab paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (RECIST 1.1)
ORR is defined as the percentage of patients who achieve complete response (CR) or partial response (PR) based on the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Secondary outcomes (7)
Objective response rate (irRECIST)
It will be evaluated based on the immune-related (ir) RECIST criteria.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Disease control rate
DCR is defined as the percentage of patients who achieved CR, PR and stable disease (SD), and will be evaluated based on RECIST 1.1 and the irRECIST criteria.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Duration of response (RECIST 1.1)
DoR is defined as the time from first documented objective response (CR or PR, whichever occurs first, as per RECIST v1.1) to disease progression or death, whichever occurs first.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Progression free survival (RECIST 1.1)
PFS is defined as the time from the date of first dose of study drugs to the date of the first documented disease progression (determined as per RECIST v1.1) or date of death, whichever occurs first.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Overall survival
Measured: From date of first dose until the date of death from any cause, assessed up to 24 months
Safety and tolerability by incidence, severity and outcome of adverse events
Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTCAE Version 5.0.
Dose-limiting toxicities (DLT) will be evaluated by the investigators 28 days after the first dose of study drugs in order to determine the RP2D of surufatinib in combination with KN046 and the AG regimen in phase Ib.
Measured: From first dose to within 90 days after the last dose, up to 24 months
Predictive biomarkers
To evaluate the correlation between potential biomarkers and the prognosis of patients treated with this regimen. Tumor tissue or blood samples will be examined to assess relevant parameters including MSI/dMMR status, TMB, PD-1/PD-L1/CTLA-4 expression, VEGFR/FGFR/CSF-1R expression, plasma ctDNA, tumor markers such as CA19-9/CEA before and after treatment, plasma concentration of sVEGFR2, VEGF, FGF23, FGF2, M-CSF, etc.
Measured: From date of screening until the date of death, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2023
- Study start1 Nov 2023
- Primary completion1 Nov 2024 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Locally Advanced or Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fudan University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05832892
- Sponsor's protocol ID
- ZSPAC-02
- Status last verified
- Jun 2023
- First submitted
- 16 Apr 2023
- Last updated
- 14 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The IPD will not be shared with other researchers in order to protect patients' privacy.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of Surufatinib in Combination With KN046 and AG Regimen Chemotherapy for the First-Line Treatment of Unresectable Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT05832892
- Acronym / sponsor ID
- ZSPAC-02
- Keywords
- Pancreatic Cancer, Surufatinib, KN046, Nab-paclitaxel, Gemcitabine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Collaborators
- Fudan University
- Study start
- 1 Nov 2023 (actual)
- Primary completion
- 1 Nov 2024 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 27 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Advanced pancreatic cancer is a highly aggressive and fatal disease with an extremely low 5-year survival rate. Combined chemotherapy is the mainstay of treatment for patients with unresectable advanced pancreatic cancer, and the combination of nab-paclitaxel and gemcitabine (AG regimen) has been one of the most commonly used regimens for more than a decade. However, chemo-resistance often occurs within half a year and the efficacy remains unsatisfied with an overall survival of only 9~11 months.
Immune checkpoint inhibitors (ICIs) such as anti-PD-1/L1 antibody and anti-CTLA-4 antibody have demonstrated encouraging anti-tumor efficacy in multiple solid tumors including lung cancer, gastric cancer, and esophageal cancer, while obtained controversial results when combined with chemotherapy in pancreatic cancer. Recently, the immune-suppression tumor microenvironment (TME) of pancreatic cancer has been described in several pre-clinical studies, which may explain the resistance against ICIs and chemotherapy.
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific antibody with innovative designs include a proprietary CTLA-4 domain antibody with a significantly improved safety profile, a bispecific antibody fused with PD-L1 antibody targeting the TME with high PD-L1 expression. Recent clinical studies have shown promising anti-tumor activity of KN046 in pancreatic cancer.
Surufatinib, also known as HMPL-012 or Sulfatinib, is a small molecular tyrosine kinase inhibitor (TKI) targeting the Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor (FGFR) and Colony Stimulating Factor-1 Receptor (CSF-1R), which has a dual mechanism of action of anti-angiogenesis and regulation of immune microenvironment. Previous studies have suggested synergic effect of surufatinib in combination with anti-PD-1 antibodies.
This phase Ib/II clinical trial is intended to investigate the activity and safety of the combination of surufatinib combined with KN046 and the AG regimen chemotherapy as first-line treatment in patients with unresectable locally advanced or metastatic pancreatic cancer.
Detailed description
Advanced pancreatic cancer is a highly aggressive and fatal disease with an extremely low 5-year survival rate. Combined chemotherapy is the mainstay of treatment for patients with unresectable advanced pancreatic cancer, and the combination of nab-paclitaxel and gemcitabine (AG regimen) has been one of the most commonly used regimens for more than a decade. However, chemo-resistance often occurs within half a year and the efficacy remains unsatisfied with an overall survival of only 9~11 months.
Immune checkpoint inhibitors (ICIs) such as anti-PD-1/L1 antibody and anti-CTLA-4 antibody have demonstrated encouraging anti-tumor efficacy in multiple solid tumors including lung cancer, gastric cancer, and esophageal cancer, while obtained controversial results when combined with chemotherapy in pancreatic cancer. Recently, the immune-suppression tumor microenvironment (TME) of pancreatic cancer has been described in several pre-clinical studies, which may explain the resistance against ICIs and chemotherapy.
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific antibody with innovative designs include a proprietary CTLA-4 domain antibody with a significantly improved safety profile, a bispecific antibody fused with PD-L1 antibody targeting the TME with high PD-L1 expression. Recent clinical studies have shown promising anti-tumor activity of KN046 in pancreatic cancer.
Surufatinib, also known as HMPL-012 or Sulfatinib, is a small molecular tyrosine kinase inhibitor (TKI) targeting the Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor (FGFR) and Colony Stimulating Factor-1 Receptor (CSF-1R), which has a dual mechanism of action of anti-angiogenesis and regulation of immune microenvironment. Previous studies have suggested synergic effect of surufatinib in combination with anti-PD-1 antibodies.
This phase Ib/II clinical trial is intended to investigate the activity and safety of the combination of surufatinib combined with KN046 and the AG regimen chemotherapy as first-line treatment in patients with unresectable locally advanced or metastatic pancreatic cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| surufatinib + KN046 + nab-paclitaxel + gemcitabine | Experimental | Drug: surufatinib, Drug: KN046, Drug: gemcitabine, Drug: Nab paclitaxelIn the phase Ib of dose escalation, all patients enrolled will receive: nab-paclitaxel at 125 mg/m2 on days 1 and 8, gemcitabine at 1000 mg/m2 on days 1 and 8, KN046 at 5 mg /kg on day 1, plus surufatinib per cohort escalation assignment starting with 200 mg. The combination treatment repeats every 3 weeks, until disease progression, death, intolerable toxicity, or withdrawal of informed consent. Dose-limiting toxicity will be evaluated 28 days after first dose to determine the recommended phase 2 dose (RP2D) of surufatinib. Patients enrolled in the phase II of dose expansion will receive the combination regimen of nab-paclitaxel plus gemcitabine plus KN046 plus surufatinib as determined in the phase Ib. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed informed content obtained prior to treatment.
- Male or female, age ≥ 18 years and ≤ 75 years.
- Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that originated from the pancreatic ductal epithelial, with image-documented unresectable locally advanced or distant metastatic disease.
- Patients have received no previous local treatment such as surgery, radiotherapy, ablation, or any systemic treatment for advanced/metastatic pancreatic cancer, including neoadjuvant and/or adjuvant therapy.
- Have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Key exclusion criteria (27 listed)
- Adverse events (AEs) due to previous anti-tumor therapy have not recovered to CTCAE Grade ≤1 (except for hair loss, skin pigment changes, or Grade ≤ 2 neurotoxicity).
- Other malignancies diagnosed within past 5 years (except basal cell carcinoma of the skin or squamous cell carcinoma and carcinoma in situ of the cervix that have been effectively controlled).
- Presence of central nervous system (CNS) metastases at screening, or have a history of CNS metastases.
- Patients who have received approved systemic anti-tumor therapy within 4 weeks before the first dose of study drugs, including chemotherapy, biological therapy, targeted therapy, hormone therapy, traditional Chinese medicine therapy (with clear anti-tumor indications in the label), etc.
- Patients who have received radical radiotherapy (including radiotherapy involving > 25% bone marrow) within 4 weeks prior to the first study drugs reception; Or brachytherapy (e.g., implanted radioparticles) within 60 days prior to the first dose of the study drugs; Or palliative radiotherapy for bone metastases within 1 week prior to first dose of the study drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| surufatinibAlso: HMPL-012, SulfatinibIn phase Ib, surufatinib will be orally administrated 200 mg once a day (QD) or 250 mg QD per cohort escalation assignment on a 21-day cycle. In phase II, surufatinib will be orally administrated at RP2D as determined in phase Ib. | Drug | surufatinib + KN046 + nab-paclitaxel + gemcitabine |
| KN046Nab-paclitaxel will be administrated at 125 mg/m2 intravenously on day 1 and 8 of each 21-day cycle. | Drug | surufatinib + KN046 + nab-paclitaxel + gemcitabine |
| gemcitabineAlso: GEMZARGemcitabine will be administrated at 1000 mg/m2 intravenously on day 1 and 8 of each 21-day cycle. | Drug | surufatinib + KN046 + nab-paclitaxel + gemcitabine |
| Nab paclitaxelAlso: nanoparticle albumin-bound paclitaxel, Abraxane, ABI-007Nab-paclitaxel will be administrated at 125 mg/m2 intravenously on day 1 and 8 of each 21-day cycle. | Drug | surufatinib + KN046 + nab-paclitaxel + gemcitabine |
Primary outcome
Objective response rate (RECIST 1.1)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
ORR is defined as the percentage of patients who achieve complete response (CR) or partial response (PR) based on the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
7 secondary outcomes
Objective response rate (irRECIST)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Disease control rate
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Duration of response (RECIST 1.1)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Progression free survival (RECIST 1.1)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months
Overall survival
Time frame: From date of first dose until the date of death from any cause, assessed up to 24 months
Safety and tolerability by incidence, severity and outcome of adverse events
Time frame: From first dose to within 90 days after the last dose, up to 24 months
Predictive biomarkers
Time frame: From date of screening until the date of death, assessed up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Individual participant dataSharing planned: No. The IPD will not be shared with other researchers in order to protect patients' privacy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing surufatinib, KN046 and gemcitabine in people with Unresectable Locally Advanced or Metastatic Pancreatic Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wen-Quan Wang, MD, PhD (+86 21 31587861, wang.wenquan@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (RECIST 1.1) (time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2024.