Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Pancreatic Cancer

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Yao Zhang

Duowu Zou

Yao Zhang, M.D.

Duowu Zou, M.D.

The early diagnosis rate of pancreatic cancer is low and most patients rely on palliative chemotherapy. However, the clinical benefit and objective response rate (ORR) of patients with first-line chemotherapy are low. Therefore,it is essential to develop new therapies to improve the survival of patients with pancreatic cancer.

In this study, patients with advanced pancreatic cancer who failed in the first-line chemotherapy will be included to receive anti-PD-1 monoclonal antibody treatment, and a high-throughput study with a small sample size will be carried out by using multiomics technology to capture the heterogeneity of response to PD-1 therapy in patients with pancreatic cancer.The investigators choose two time points: after chemotherapy failure (before PD-1 therapy) and during efficacy evaluation（after PD-1 therapy）, to obtain in situ samples of pancreatic cancer tissues by EUS-FNA.The samples are tested by dynamic multi-omics studybefore and after treatment (including genomics, transcriptomics, metabonomics, proteomics, etc.).And combining the results with the drug reaction and clinical outcome of patients for a comprehensive analysis.The purpose of this study is to explore the potential biomarkers or omics of PD-1 therapy and lay the foundation for building a model to predict the effect of PD-1 therapy in patients with advanced pancreatic cancer.

n situ tissue samples of pancreatic cancer by EUS-FNAare immediately sent to the laboratory for sequencing.

Serum, plasma and peripheral blood mononuclear cells (PBMC) are isolated from peripheral blood samples; Serum and plasma are stored in - 80 ℃ refrigerator, and PBMC are stored in liquid nitrogen.

Biological samples of all patients are kept in a regulated biological sample bank.

Influence Factors of PD-1 Therapeutic Efficacy in Advanced Pancreatic Cancer

Exploring the Influence Factors of the Efficacy of PD-1 Monoclonal Antibody Therapy in Advanced Pancreatic Cancer After Failure of First-line Chemotherapy by Using Multiomics Technology

The time from random to the first occurrence of disease progression or death from any cause.

The percentage of cases with remission and disease stability after treatment in the whole evaluable cases.

According to the European Organization for research and treatment of cancer (EORTC) quality of life core scale EORTC QLQ-C30 (V3.0 Chinese version)，evaluating the quality of life (QOL)

Ruijin Hospital

Chief physician

Carcinoma

Carcinoma, Ductal

Carcinoma, Pancreatic Ductal

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Immunologic Factors

MEDI4736 monotherapy

tremelimumab+MEDI4736

Eileen M O'Reilly, M.D

A Phase II Open-Label, Multi-Center Study of MEDI4736 Evaluated as Single Agent or in Combination with Tremelimumab in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

This is a Phase II, open-label, multi-center study to determine the efficacy and safety of MEDI4736 evaluated as single agent or in combination with tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) whose disease has progressed on fluoropyrimidine containing or gemcitabine-containing first-line chemotherapy.This study will consist of Part A, lead-in, as well as a possible expansion Part B.

Phase II Study of MEDI4736 Monotherapy or in Combinations With Tremelimumab in Metastatic Pancreatic Ductal Carcinoma

A Phase II Open-Label, Multi-Center Study of MEDI4736 Evaluated as Single Agent or in Combination With Tremelimumab in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

ORR was defined as the percentage of patients with at least one visit response of confirmed complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have had reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, taking as reference the baseline sum of diameters. A confirmed response meant that a response of CR/PR was recorded at 1 visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit and not less than 4 weeks after the visit when response was first observed with no evidence of progression between the initial and CR/PR confirmation visits. Results are reported as percentage of patients with a confirmed response and percentage of patients with confirmed or unconfirmed responses (i.e., including single visit responses).

PFS was defined as the time from the date of randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient had withdrawn from randomised therapy or had received another anti-cancer therapy prior to progression. Results are reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique.

PFS was defined as the time from the date of randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient had withdrawn from randomised therapy or had received another anti-cancer therapy prior to progression. PFS rates were calculated using Kaplan-Meier estimates of the cumulative probability of PFS. The PFS rate at 3 months and 6 months was equivalent to the percentage of patients with PFS after 3 months and 6 months, respectively.

OS was defined as the time from the date of randomisation until death due to any cause. Results are reported as median OS, calculated using the Kaplan-Meier technique.

OS was defined as the time from the date of randomisation until death due to any cause. OS rates were calculated using Kaplan-Meier estimates of the cumulative probability of survival at each indicated time period. The OS rate at 6 months and 12 months was equivalent to the percentage of patients with OS after 6 months and 12 months, respectively.

BoR was calculated based on the overall visit responses from each RECIST assessment. It was the best response a patient had following date of first dosing but prior to starting any subsequent cancer therapy and prior to RECIST progression or last evaluable assessment in absence of RECIST progression. Categorisation of BoR was based on RECIST using the following response categories: CR and PR for status of 'Response'; Stable Disease (SD) ≥6 weeks, Progressive Disease (PD) and Not Evaluable (NE) for status of 'Non-response'. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the sum of diameters of TLs taking as reference the smallest sum on study. NE was only relevant if any of the TLs were not assessed or not evaluable or had a lesion intervention at this visit. Results are reported as number of patients with BoR for each of the indicated categories.

DCR at 3 months was defined as the percentage of patients who have a BoR of CR or PR in the first 3 months or who have demonstrated SD for a minimum interval of 13 weeks following the start of treatment. DCR at 6 months was defined as the percentage of patients who have a BoR of CR or PR in the first 6 months or who have demonstrated SD for a minimum interval of 26 weeks following the start of treatment. DCR at 12 months was defined as the percentage of patients who have a BoR of CR or PR in the first 12 months or who have demonstrated SD for a minimum interval of 52 weeks following the start of treatment. Results are reported as the percentage of patients with disease control for each of the indicated categories.

To evaluate PK, blood samples were collected pre- and post-dose and durvalumab (MEDI4736) concentrations in serum were determined. On Day 1 of Cycles 1, 4 and 7 (Weeks 0, 12 and 24), PK samples were collected pre-dose (within 60 minutes prior to treatment with any IP) and post-dose at the end of infusion (within 10 minutes of end of infusion of durvalumab and within 10 minutes of end of infusion of tremelimumab \[for patients receiving durvalumab plus tremelimumab\]). On Day 1 of Cycle 2 (Week 4), PK samples were collected pre-dose (within 60 minutes prior to treatment with any IP) only. The 3-month follow-up sample for durvalumab was relative to the respective last dose. Results are reported as mean pre- or post-dose durvalumab concentrations as indicated by the individual categories (1 cycle=4 weeks). Samples below lower limit of quantification were treated as missing in the analyses.

To evaluate PK, blood samples were collected pre- and post-dose and tremelimumab concentrations in serum were determined. On Day 1 of Cycles 1 and 4 (Weeks 0 and 12), PK samples were collected pre-dose (within 60 minutes prior to treatment with any IP) and post-dose at the end of infusion (within 10 minutes of end of infusion of tremelimumab). On Day 1 of Cycle 2 (Week 4), PK samples were collected pre-dose (within 60 minutes prior to treatment with any IP) only. The 3-month follow-up sample for tremelimumab was relative to the respective last dose. Results are reported as mean pre- or post-dose tremelimumab concentrations as indicated by the individual categories (1 cycle=4 weeks). Samples below lower limit of quantification were treated as missing in the analyses.

ADA prevalence was the proportion of the ADA evaluable set who had an ADA positive result at any point in time, baseline or post-baseline. ADA incidence (treatment-emergent ADA) was the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA positive patients as a proportion of the evaluable patient population. Treatment-boosted ADA was defined as baseline positive ADA titre boosted to a 4-fold or higher level following IP administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Results are reported as number of patients with detectable anti-durvalumab antibodies satisfying each of the indicated categories. Note: 'positive' is denoted by 'pos' in some category titles.

ADA prevalence was the proportion of the ADA evaluable set who had an ADA positive result at any point in time, baseline or post-baseline. ADA incidence (treatment-emergent ADA) was the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA positive patients as a proportion of the evaluable patient population. Treatment-boosted ADA was defined as baseline positive ADA titre boosted to a 4-fold or higher level following IP administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Results are reported as number of patients with detectable anti- tremelimumab antibodies satisfying each of the indicated categories. Note: 'positive' is denoted by 'pos' in some category titles.

AstraZeneca

TEAE definition: onset date ≥ first dose of IP (or pre-treatment AEs increasing in severity ≥ first dose) and ≤ the last dose of IP + 90 days or ≤ start date of subsequent therapy (whichever occurred first). All-cause mortality definition: death due to any cause (including disease progression of pancreatic cancer) up to 90 days after last dose of IP or until start of subsequent therapy, whichever occurred first.

Patients in the durvalumab (MEDI4736) plus tremelimumab combination therapy arm received 1.5 g durvalumab and 75 mg tremelimumab via IV infusion q4w over a 16-week treatment period. Patients then continued with durvalumab monotherapy at 1.5 g q4w, beginning at Week 16, 4 weeks after the last dose of combination therapy, up to a total of 9 additional doses, with the final dose at Week 48.

For the combination therapy, tremelimumab was administered first; the durvalumab infusion was started approximately 1 hour after the end of the tremelimumab infusion.

Durvalumab (MEDI4736) Plus Tremelimumab

Patients in the durvalumab (MEDI4736) monotherapy arm received 1.5 g durvalumab via IV infusion q4w over a 48-week treatment period (up to 13 doses).

Durvalumab (MEDI4736) Monotherapy

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

All patients in the FAS who were randomised to treatment were included in the baseline analysis.

Study consisted of Part A Lead-in and 2 possible options for Part B: non-randomised expansion or randomised controlled trial. Criteria to open either option for Part B were not met and study was closed prematurely. Only Part A was conducted.

Global Clinical Lead

Confirmed responses only

Confirmed and unconfirmed responses

The FAS included all randomised patients.

Objective Response Rate (ORR) in All Patients Using Investigator Assessments According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Progression-free Survival (PFS) Using Investigator Assessments According to RECIST 1.1

PFS rate at 3 months

PFS rate at 6 months

PFS Rate at 3 Months and at 6 Months

Overall Survival (OS)

Survival rate at 6 months

Survival rate at 12 months

Survival Status, Presented as OS Rate, at 6 Months and at 12 Months

Response: Total

Response: CR

Response: PR

Non-response: Total

Non-response: Stable disease ≥6 weeks

Non-response: Progression of disease

Non-response: Not evaluable

Best Objective Response (BoR) Using Investigator Assessments According to RECIST 1.1

At 3 months

At 6 months

At 12 months

Disease Control Rate (DCR) Using Investigator Assessments According to RECIST 1.1

Cycle 1, Day 1, pre-infusion (Day 1)

Cycle 1, Day 1, post-infusion (Day 1)

Cycle 2, Day 1, pre-infusion (Day 29)

Cycle 4, Day 1, pre-infusion (Day 85)

Cycle 4, Day 1, post-infusion (Day 85)

Cycle 7, Day 1, pre-infusion (Day 169)

Cycle 7, Day 1, post-infusion (Day169)

3-month follow-up

The PK analysis set included all patients who received at least 1 dose of IP, and had PK sampling data post-dose without important deviations or events to affect PK (n=64). Only patients with data available at the timepoints of testing were included in the analyses.

Pharmacokinetics (PK) of Durvalumab (MEDI4736)

PK of Tremelimumab

ADA prevalence

ADA incidence

ADA pos post-baseline and pos at baseline

ADA pos post-baseline and not detected at baseline

ADA not detected post-baseline and pos at baseline

Treatment-boosted ADA

Persistent positive

Transient positive

Never positive

The ADA evaluable set included all patients in the safety analysis set (i.e. those who had received any IP) who had non-missing baseline ADA data and at least 1 non-missing post-baseline ADA result.

Presence of Antidrug Antibodies (ADAs) for Durvalumab (MEDI4736)

Presence of ADAs for Tremelimumab

Patients in the durvalumab (MEDI4736) plus tremelimumab combination therapy arm received 1.5 grams (g) durvalumab and 75 milligrams (mg) tremelimumab via intravenous (IV) infusion every 4 weeks (q4w) over a 16-week treatment period. Patients then continued with durvalumab monotherapy at 1.5 g q4w, beginning at Week 16, 4 weeks after the last dose of combination therapy, up to a total of 9 additional doses, with the final dose at Week 48.

For the combination therapy, tremelimumab was administered first; the durvalumab infusion was started approximately 1 hour after the end of the tremelimumab infusion.

Overall Study

The early symptoms of pancreatic cancer are not obvious, and the early diagnosis rate is low. For most patients with pancreatic cancer,palliative chemotherapy is the only choice .At present, The guidance of NCCN guidelines on the selection of chemotherapy regimens for patients with advanced pancreatic cancer is only based on the physical condition(the ECOG score), which is one of the important reasons for the poor efficacy of chemotherapy in patients with advanced pancreatic cancer.Therefore, it is urgent to group pancreatic cancer patients according to tumor molecular typing and heterogeneity of response to chemotherapy drugs accurately,so as to guide the personalized treatment of patients.

Based on the limitations of existing studies and the needs of clinical patients, the investigators chose two time points: after the diagnosis of pancreatic cancer (before the first-line chemotherapy), and after chemotherapy evaluation in this study, to obtain in situ samples of pancreatic cancer tissues by EUS-FNA.The samples are detected by dynamic multi-omics study before and after treatment(including genomics, transcriptomics, proteomics, metagenomics, etc.).Combined with the drug reaction and clinical outcome of patients, a comprehensive model is established to predict the clinical outcome of patients with PDAC and the choice of chemotherapy regimens, so as to screen the pancreatic cancer patients who are most likely to benefit from different chemotherapy regimens, and lay the foundation for the development of individual chemotherapy for advanced pancreatic cancer.

in situ tissue samples of pancreatic cancer by EUS-FNAare immediately sent to the laboratory for sequencing.

Serum, plasma and peripheral blood mononuclear cells (PBMC) are isolated from peripheral blood samples; Serum and plasma are stored in - 80 ℃ refrigerator, and PBMC are stored in liquid nitrogen.

Biological samples of all patients are kept in a regulated biological sample bank.

Clinical and Multiomics Study of First-line Chemotherapy for Advanced Pancreatic Cancer

Clinical and Multiomics Study of First-line Chemotherapy for Advanced Pancreatic Cancer：a Prospective Single-center Research Trial

The difference of progression free survival (PFS)

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

After 4-6 cycles of induction therapy with gemcitabine and nab-paclitaxel plus surufatinib, if become operable, the therapy will be continued for another 6 months after surgery; if not operable, the therapy will be also continued as long as no PD during induction therapy. If PD occurs, it will enter second-line therapy.

Surufatinib capsules: oral, once daily. Combination treatment period: 200 mg each time, every 4 weeks for a treatment cycle(Q4W). If all the chemotherapy drugs were stopped during the maintenance treatment period, only surufatinib was left, the dose of Surufatinib could be increased to 300 mg per dose according to the patient\&#39;s condition.

Gemcitabine: iv, 1000 mg/m2, days 1, 8, and 15 of each treatment cycle, Q4W. Paclitaxel (albumin-bound), iv, 125mg/m2, on days 1, 8 and 15 of each treatment cycle, Q4W.

All they will be used until disease progression, death, intolerable toxicity, initiation of new antineoplastic therapy, withdrawal of consent, loss to follow-up, or any other protocol-specified event requiring treatment discontinuation or study closure, whichever occurred first.

But If surgical resection was performed, they will be only maintained for 6 months after surgery.

surufatinib combined with gemcitabine plus nab-paclitaxel

Heshui Wu

To evaluate the efficacy and safety of surufatinib combined with gemcitabine plus nab-paclitaxel in patients with locally advance d pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Currently, there is no standard treatment for locally unresectable PDAC, and clinical research and conversion therapy are encouraged by guidelines. Whether it is conversion or palliative chemotherapy, in fact, the choice of chemotherapy is based on the existing first-line regimens of metastatic PDCA. Gemcitabine combined with nab-paclitaxel is one of the preferred first-line chemotherapy regimens for metastatic or locally advanced PDAC. However, the conversion rate of gemcitabine combined with nab-paclitaxel is not ideal according to the current results. The aim of this study is to investigate whether the combination of gemcitabine and nab-paclitaxel with surufatinib can improve the surgical conversion rate.

This is a prospective, single-arm exploratory clinical study. A safety run-in period of 6 patients will be set. After 4-6 cycles of induction therapy with gemcitabine and nab-paclitaxel plus surufatinib, if become operable, the therapy will be continued for another 6 months after surgery; if not operable, the therapy will be also continued as long as no PD during induction therapy. If PD occurs, it will enter second-line therapy. Surufatinib capsule will be administered orally 200mg, once daily, a 4-week treatment cycle(Q4W) during combined with gemcitabine and nab-paclitaxel. If all chemotherapy drugs are stopped during the maintenance treatment period and only surufatinib is left, the dose of surufatinib can be increased to 300 mg per dose according to the patient's condition. Gemcitabine and nab-paclitaxel plus surufatinib will be used until disease progression, death, intolerable toxicity, initiation of new antineoplastic therapy, withdrawal of informed consent, loss of follow-up, and other conditions that require treatment discontinuation or the study is completed. Whichever comes first. If surgical resection was performed, it will be maintained for 6 months.

Surufatinib Combined With Gemcitabine Plus Nab-paclitaxel in Locally Advanced Pancreatic Cancer

An Exploratory Clinical Study of Surufatinib Combined With Gemcitabine Plus Nab-paclitaxel in Patients With Locally Advanced Pancreatic Cancer

Surgical conversion rate, defined as the proportion of patients who achieved gross complete resection after 4-6 cycles of study induction therapy.

Objective response rate (ORR) was defined as complete response (CR) and partial response (PR) proportion of participants.

Disease control rate (DCR) was defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD).

R0 surgical conversion rate: defined as the proportion of patients who achieved R0 surgical resection after 4-6 cycles of study induction therapy.

Progression-free survival (PFS), defined as the time from the first initiation of study regimen treatment to the first imaging disease progression or the time of death, whichever occurs first.

Overall survival (OS), defined as the time from the first initiation of the study regimen to death from any cause time.

From the first dose to the end of the study treatment, treatment emergent adverse event（TEAE）、study drug-related adverse event (TRAE) and serious adverse event （SAE) will be summarized and incidence will be calculated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Influence Factors of PD-1 Therapeutic Efficacy in Advanced Pancreatic Cancer	NCT05201729	Pancreatic Duct...		18 Years -	Ruijin Hospital
Phase II Study of MEDI4736 Monotherapy or in Combinations With Tremelimumab in Metastatic Pancreatic Ductal Carcinoma	NCT02558894	Metastatic Panc...	MEDI4736 monoth... tremelimumab+ME...	18 Years -	AstraZeneca
Clinical and Multiomics Study of First-line Chemotherapy for Advanced Pancreatic Cancer	NCT05168254	Pancreatic Duct...		18 Years -	Ruijin Hospital
Surufatinib Combined With Gemcitabine Plus Nab-paclitaxel in Locally Advanced Pancreatic Cancer	NCT06361030	Pancreatic Canc... Pancreatic Canc... Pancreatic Duct...	surufatinib com...	18 Years - 75 Years	Wuhan Union Hospital, China
Influence Factors of PD-1 Therapeutic Efficacy in Advanced Pancreatic Cancer	NCT05201729	Pancreatic Duct...		18 Years -	Ruijin Hospital
Influence Factors of PD-1 Therapeutic Efficacy in Advanced Pancreatic Cancer	NCT05201729	Pancreatic Duct...		18 Years -	Ruijin Hospital
Surufatinib Combined With Gemcitabine Plus Nab-paclitaxel in Locally Advanced Pancreatic Cancer	NCT06361030	Pancreatic Canc... Pancreatic Canc... Pancreatic Duct...	surufatinib com...	18 Years - 75 Years	Wuhan Union Hospital, China

Spots Global Cancer Trial Database for pancreatic ductal adenocarcinoma, pdac