Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Bevacizumab

Angiogenesis Inhibitors

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Growth Inhibitors

Participants receive bevacizumab 7.5mg/kg and tripleitriumab 240mg in day 1 intravenously every 3week until disease progression or unacceptable toxicity

Tripleitriumab

Hanguang Hu, M.D.

Ying Yuan, M.D.

This is a single-arm,open-label, prospective, single-center Study of QL1101 and JS001 in patients with pMMR/MSS refractory metastatic colorectal cancer.

QL1101 is a biosimilar of bevacizumab (Avastin) produced and provided by Qilu Pharmaceutical Co., Ltd., which has been marketed in China.It's a humanized monoclonal IgG1 antibody prepared by recombinant DNA technology. By binding to human vascular endothelial growth factor (VEGF), it inhibits the binding of VEGF to its receptor, blocks the signal transduction pathway of angiogenesis, and inhibits tumor cell growth. Be produced and provided by Shanghai Junshi Bioscience Co., Ltd. ,JS001(Tripleitriumab) is the first China-developed humanized monoclonal antibody against programmed death 1 (PD-1) approved for marketing in China.

Antiangiogenic drugs combined with PD-1 monoclonal antibodies may reverse the insensitivity of pMMR/MSS refractory colorectal cancer to PD-1 inhibitors.

The primary objective of this study is to investigate the safety and efficacy of the subjects who given the combination therapy.

QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer

QL1101A,a Biosimilar of Bevacizumab,in Combination With JS001,a Anti-pd-1 Antibody in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer: a Single-arm,Open-Label, Prospective, Single-center Study

Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. PFS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%.

Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. OS will be tested at the one-sided 10% level.

Best objective response will be evaluated via RECIST 1.1 and iRECIST criteria. Will be compared using Fisher's exact tests with a one-sided type I error rate of 2.5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.

Disease control is defined as maintaining Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) as the tumor assessment result during the defined time window. DCR (percentage) is defined as number of patients with success of disease control divided by total number of patients in the analysis population multiplied by 100, excluding patients who refuse treatment before the initiation of any treatment. CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by ≥50% of previously involved sites from nadir, SD: Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD

The distribution of DOR by treatment group will be estimated using the method of Kaplan-Meier. Six and 12 month durable response (i.e. maintaining CR or PR without progressive disease \[PD\]) rates by treatment group with confidence intervals will be estimated based on Kaplan-Meier curves. The HR with confidence interval will be estimated based on stratified Cox models (stratified by levels of stratification factors), without and with adjusting for baseline clinical/pathological factors.CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by ≥50% of previously involved sites from nadir

Qilu Pharmaceutical Co., Ltd.

Shanghai Junshi Bioscience Co., Ltd.

Second Affiliated Hospital, School of Medicine, Zhejiang University

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Neuroendocrine Tumors

Small Cell Lung Carcinoma

Carcinoma, Neuroendocrine

Sarcoma

Mesothelioma

Mesothelioma, Malignant

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplasms, Connective and Soft Tissue

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumor

Small Cell Lung Cancer

Soft Tissue Sarcoma

Malignant Mesothelioma

Neuroepithelioma

Tislelizumab

The trial will include 8 cohorts of patients, with each cohort considered as a single-arm; all patients enrolled will be treated with regorafenib at a dose of 90 mg orally once daily, on days 1 to 21 of a 28 cycle in combination with tislelizumab 300 mg intravenously day 1 (of a 28 day cycle).

Regorafenib 30 mg/tablet + Tislelizumab 100 mg/10 ml vial

Regorafenib in combination with Tislelizumab

Josep Tabernero

REFIT-MSS is a non-randomized, multicenter, open-label, multi-cohort, 2-stage, phase II trial to evaluate the efficacy and safety of regorafenib in combination with tislelizumab (referred as Rego-Tisle) in adult patients with select advance, previously treated, Mismatch Repair-Proficient/Microsatellite (pMMR/MSS) stable solid cancers.

The multi-cohort design will allow for the examination of 8 separate cohorts of different cancers to determine whether further examination may be warranted in the individual indications.

This is a non-randomized, multicenter, open-label, multi-cohort, phase II trial to evaluate the efficacy and safety of Rego-Tisle in adult patients with solid tumors that are advanced, pretreated and refractory to standard therapy. Approximately 322 evaluable patients (between 15 and 82 per cohort) in around 65 sites will be enrolled to power the trial efficiently to measure the primary endpoint, Progression Free Survival at 6 months (PFS-6).

Patients should have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors guidelines version 1.1 (RECIST 1.1), an Eastern Cooperative Oncology Group Performance Scale (ECOG PS) 0-1, and adequate organ function.

The trial will include patients who had been diagnosed with a histologically or cytologically confirmed solid tumor belonging to any of the types in the cohorts to be enrolled. To be eligible, patient must meet the criteria for tumor type, stage and prior anti-cancer therapy according to inclusion criteria.

The trial will include 8 cohorts of patients. Each cohort is considered as a single-arm activity-estimating sub-study with PFS-6 as the primary endpoint. A strong primary endpoint signal seen in a cohort may allow for expansion of the cohort, independently of the status of the other cohorts. Similarly, a cohort may be opened and/or closed for enrollment independently of others.

Regorafenib With Tislelizumab in Patients With Selected Mismatch Repair-Proficient/Microsatellite Stable Cancers

An Open-label, Phase II, Multi-cohort, 2-stage Trial to Evaluate the Efficacy and Safety of Regorafenib in Combination With Tislelizumab in Patients With Selected Mismatch Repair-Proficient/Microsatellite Stable Pretreated Solid Cancers

PFS-6 is defined as the proportion of patients who remained free of PFS event (disease progression or death) at 6 months from the date of enrollment.

Defined as the proportion of patients who have a complete response (CR) or partial response (PR) based on investigator assessment.

Defined as the proportion of patients who have CR, PR, or stable disease (SD) according to RECIST 1.1, as per investigator assessment.

Defined as the time (in months) from first documentation of response (PR or CR) to progressive disease (PD) or death, based on investigator assessment or death, in patients who had best overall response of CR or PR.

Defined as as the ratio of time to progression (TTP) with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line.

Defined as time from date of enrollment to date of death due to any cause. Median OS, OS at 6 months (OS-6) and OS at 12 months (OS-12) will be evaluated.

In metastatic castration-resistant prostate cancer (mCRPC) cohort only; defined as the time from the date of enrollment to the date of PSA progression based on Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria

Frequency and severity of AEs and laboratory abnormalities

Bayer

Novartis

Translational Research in Oncology

Infections

Virus Diseases

Retinitis Pigmentosa 15

Atezolizumab

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

Genetically modified herpes simplex type 1 virus

atezolizumab

bevacizumab

May Cho, MD

This is an open-label, Phase 2 clinical trial evaluating therapy with an oncolytic immunotherapy (RP2 or RP3) in combination with atezolizumab and bevacizumab in patients with advanced Microsatellite Stable and Mismatch Repair Proficient Colorectal Carcinoma.

RP2 and RP3 are selectively replication competent herpes simplex viruses 1 (HSV-1) that express exogenous genes (RP2: GM-CSF, GALV, and anti-CTLA-4; RP3: GALV, and anti-CTLA-4 hCD40L, and h4-1BBL) intended for direct injection into suitable nonneurological solid tumors. They are genetically engineered to provide direct oncolytic tumor destruction combined with the induction of a systemic antitumor immune response.

This study will evaluate whether the use of oncolytic immunotherapy, either with RP2 or RP3, can provide meaningful efficacy in combination with an anti-PD-L1 therapy (atezolizumab) and anti-VEGF therapy (bevacizumab) in patients with advanced MSS and pMMR CRC.

RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC

A Phase 2 Clinical Trial Investigating Oncolytic Immunotherapy in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With Advanced Microsatellite Stable and Mismatch Repair Proficient Colorectal Carcinoma

Percentage of subjects achieving objective response (complete response + partial response).

Percentage of subjects with TEAEs and SAEs

Overall survival is defined as the time from the first day of study treatment to the date of death by any cause

Progression-free survival is defined as the time from the first day of study treatment to the date of progression of disease, which was subsequently confirmed, or death by any cause, whichever occurs first

Duration of response is defined as the time from documented response until the date of progression of disease, which was subsequently confirmed or with no further follow-up, or death due to any cause, whichever occurs first

Duration of clinical benefit is defined as the time from the first day of study treatment to last progression of disease, which was subsequently confirmed or with no further follow-up for response, or death due to any cause, whichever occurs first, for subjects who achieve complete response, partial response, or stable disease

Percentage of subjects achieving a complete response

Roche Pharma AG

Replimune Inc.

Rectal Neoplasms

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Capecitabine

Oxaliplatin

Celecoxib

Antimetabolites

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

articipants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w and celecoxib, 200mg, PO, BID, day1-21, q3w. Treatment repeats every 3 weeks for 6-8 cycles followed by surgery (total mesorectal excision, TME).

Serplilumab is an innovative monoclonal antibody targeting PD-1, developed by Shanghai Henlius Biotech, Inc.

300 mg, q3w

Serplilumab

Kefeng Ding, doctor

Jinjie He, Doctor

Kefeng Ding, Doctor

Colorectal cancer of Mismatch Repair-proficient (pMMR)/ Microsatellite Stability (MSS) accounts for approximately 85% of all colorectal cancer patients, which might be insensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy, such as CAPEOX regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Celecoxib, a COX-2 inhibitor, can improve the immune microenvironment and have a potential to synergy with immunotherapy. Chemotherapy can improve the immunogenicity of cancer cells that might enhance the efficacy of immunotherapy. The aim of this study is to explore whether chemotherapy and cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could improve efficacy for resectable colorectal cancer patient with the pMMR/MSS phenotype.

Serplulimab Combined With CAPEOX + Celecoxib as Neoadjuvant Treatment for Locally Advanced Rectal Cancer

A Phase II Study to Explore the Neoadjuvant Treatment of Serplulimab Combined With CAPEOX + Celecoxib in the Treatment of Locally Advanced Rectal Cancer

Proportion of patients experiencing a pCR to perioperative PD-1 antibody

The proportion of patients experiencing a major pathological response to perioperative PD-1 antibody

Proportion of patients experiencing a cCR to perioperative PD-1 antibody

The proportion of patients achieved a complete resection with negative margin

Assessed by evaluation of treatment-related adverse events.

To detect ctDNA in peripheral blood before and after treatment

Use single cell sequence to describe changes in the microenvironment of rectal cancer before and after treatment

Zhejiang University

Professor

Hematinics

Liver Extracts

XELOX + bevacizumab + atezolizumab + SIRT (Therasphere)

Atezolizumab combined to standard chemotherapy (XELOX + bevacizumab) and targeted therapy in patients whose tumour has been made immunogenic by radiotherapy (Therasphere) and ICI (atezolizumab).

Therasphere injected to patients to promote the release of neoantigens from their tumour and convert it into an immunogenic tumour.

Therasphere

standard chemotherapy for first line treament of metastatic CRC (in pMMR and/or MSS patients)

XELOX

standard targeted therapy associated with XELOX for first line treament of metastatic CRC (in pMMR and/or MSS patients)

David Tougeron, MD, PhD

Flore Geillon, PhD

David TOUGERON, MD, PhD

Aurélie FERRU, Dr

The main objective of the SIRTCI study is to evaluate the safety and efficacy of the combination chemotherapy (XELOX: Capecitabine plus oxaliplatin), anti-angiogenic (Bevacizumab), SIRT (TheraSphere®) and ICI (Atezolizumab) in patients with CRC with predominant liver metastases. SIRTCI is a single-arm, prospective, multi-centre phase II study. The main inclusion criteria are patients with MSS mRCC with predominantly non-operable liver metastases and measurable disease. Patients with extra-hepatic metastases can be included since the objective of the study is to induce local and abscopal effects of radiotherapy combined with ICI by stimulating the anti-tumour immune response to destroy both hepatic and extra-hepatic metastases.

About 50% of patients with CRC will develop a metastatic disease. Majority of patients have unresectable disease and unresectable liver-dominant disease represents 25% of all mCRC. Morbidity and mortality in patients with mCRC are mainly due to unresectable liver metastases. In this setting, chemotherapy (doublet or triplet) plus biological agent remains the standard of care since no prospective randomized trial demonstrates the efficacy of local treatments (chemoembolization or hepatic arterial infusion chemotherapy). Actually median PFS in patients with unresectable liver-dominant mCRC is range between 9 to 12 months and more effective treatments must be evaluated.

ICI are to date ineffective in pMMR mCRC due to low level of tumor mutational load. Nevertheless, radiation induces an immunogenic cell death able to convert a "nonimmunogenic" neoplasm into an "immunogenic" neoplasm. In patients with liver-dominant mCRC SIRT has not shown survival improvement but only delayed disease progression in the liver. ICI improve efficacy of radiation both in irradiated lesions and non-irradiated lesions (abscopal effect). One explanation of the absence of PFS improvement with SIRT in first-line setting could be the progression of the extra-hepatic disease. Indeed, the rationale of SIRTCI 01 is to combine SIRT and ICI to induce an immune response and an abscopal effect against mCRC in order to improve control of hepatic disease (increase local SIRT efficacy with ICI) and extra-hepatic disease (increase abscopal effects of SIRT with ICI).

The aim of this study is therefore to demonstrate the synergistic anti-tumor efficacy of SIRT and ICI in patients with unresectable liver-dominant mCRC. Primary endpoint is PFS at 9 months. Main secondary endpoints are safety, response rate and OS. In addition, exploratory biomarker analyses will be performed in order to identify predictive factors of SIRT plus ICI efficacy. No safety issue was observed with XELOX/bevacizumab/atezolizumab and SIRT/FOLFOX/bevacizumab then the combination evaluated in SIRTCI 01 should be safe. Moreover oxaliplatin dose is decreased before SIRT treatment and bevacizumab is added only after SIRT treatment. All well-known predictive biomarkers of chemotherapy (mutational status, circulating tumor DNA) and ICI (tumor mutational load, immune response) efficacy will be analyzed. Additionally, pharmacokinetic analyses of Atezolizumab and centralized imaging review will be performed to evaluate morphologic and metabolic predictive markers (CT-scan, MRI, FDG PET/CT and Y90 PET/CT) of SIRT plus ICI efficacy.

This study will be the first one to use SIRT in order to induce immunogenic cell death and sensitivity to ICI. Combination of SIRT and ICI could increase immune abscopal anti-tumor effects of radiation. Indeed, once activated in one place (liver), the immune system can attack tumor lesions anywhere else in the body (lung, peritoneum...) through this abscopal effect.

SIRTCI 01 will provide informations on efficacy and safety of SIRT, ICI and chemotherapy combination in patients with unresectable liver-dominant mCRC. SIRT plus chemotherapy as well as chemotherapy plus ICI are well tolerated. TheraSphere® will be administered 3 or 4 days after cycle 2 or 3 of chemotherapy with adaptation of chemotherapy doses. Moreover, an interim analysis is planned to access efficacy of the strategy (first step after 22 evaluable patients included). At the time of the interim analysis, a complete review of the toxicities will be done to check the safety of the strategy and an independent data monitoring committee will monitor in real time all severe adverse events.

PFS at 9 months has been chosen as primary endpoint because it is a surrogate marker of OS. Actually median PFS in first-line setting with a doublet plus a biological agent is range from 8 to 11 months in unresectable mCRC and 9 to 12 months in unresectable liver-dominant mCRC, corresponding to a PFS of 50%-60% at 9 months. PFS is more reliable than response rate at 2-3 months given that the treatments used can induce tumor necrosis (SIRT) and/or initial pseudo-progression (ICI). In addition, most of patients will have a disease control/response at 2-3 months with this combination.As in all innovative phase II trials, this study should well include selected patients . A randomized phase II study with a large population does not seem appropriate in view of the limited literature on the safety and efficacy of this combination. The alternative clinical hypothesis to obtain 70% of patients alive and without progression at 9 months is ambitious and currently not achieved with current chemotherapies plus a biological agent.

The study will include patients with liver-dominant disease. Nevertheless, since the aim of the trial is to induce immune abscopal anti-tumor effects of radiation, patients with hepatic and extra-hepatic lesions will be included; extrahepatic lesions will be permitted if they are not symptomatic and if there is no organ dysfunction (up to 10 lesions). As ICI are very effective in dMMR mCRC (marketing authorization ongoing) it has been decided to exclude patients with dMMR mCRC.

The PFS obtain in SIRTCI 01 will provided a rationale for a randomized phase III study comparing chemotherapy alone (doublet or triplet ± biological agent) versus chemotherapy, SIRT and ICI combination in mCRC patients with unresectable liver-dominant disease.

Study to Evaluate Efficacy and Safety of Selective Internal Radiation Therapy Plus Xelox, Bevacizumab and Atezolizumab (Immune Chekpoint Inhibitor) in Patients With Liver-dominant Metastatic Colorectal Cancer

A Prospective, Multicenter, Open-label, Phase II Study to Evaluate Efficacy and Safety of Selective Internal Radiation Therapy Plus Xelox, Bevacizumab and Atezolizumab (Immune Chekpoint Inhibitor) in Patients With Liver-dominant Metastatic Colorectal Cancer

The main objective of this study is to evaluate the progression-free survival at 9 months (according to RECIST 1.1) according to the investigator.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer	NCT04527068	Refractory Meta... pMMR MSS	Bevacizumab Tripleitriumab	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Regorafenib With Tislelizumab in Patients With Selected Mismatch Repair-Proficient/Microsatellite Stable Cancers	NCT05582031	Anal Squamous C... Colorectal Neop... Soft Tissue Sar... Malignant Pleur... Small Cell Lung... Castrate Resist... Neuroendocrine ... Gastroenteropan...	Regorafenib in ...	18 Years -	Translational Research in Oncology
QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer	NCT04527068	Refractory Meta... pMMR MSS	Bevacizumab Tripleitriumab	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC	NCT05733611	Refractory Meta... pMMR MSS	RP2 RP3 atezolizumab bevacizumab	18 Years -	Replimune Inc.
QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer	NCT04527068	Refractory Meta... pMMR MSS	Bevacizumab Tripleitriumab	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Serplulimab Combined With CAPEOX + Celecoxib as Neoadjuvant Treatment for Locally Advanced Rectal Cancer	NCT05731726	pMMR MSS MSI-L Locally Advance...	Serplilumab Capecitabine Oxaliplatin Celecoxib	18 Years - 75 Years	Zhejiang University
Study to Evaluate Efficacy and Safety of Selective Internal Radiation Therapy Plus Xelox, Bevacizumab and Atezolizumab (Immune Chekpoint Inhibitor) in Patients With Liver-dominant Metastatic Colorectal Cancer	NCT04659382	Metastatic Colo... pMMR MSS Immune Checkpoi... Internal Radiot...	Atezolizumab Therasphere XELOX Bevacizumab	18 Years -	Federation Francophone de Cancerologie Digestive
Serplulimab Combined With CAPEOX + Celecoxib as Neoadjuvant Treatment for Locally Advanced Rectal Cancer	NCT05731726	pMMR MSS MSI-L Locally Advance...	Serplilumab Capecitabine Oxaliplatin Celecoxib	18 Years - 75 Years	Zhejiang University

Spots Global Cancer Trial Database for pmmr

Every month we try and update this database with for pmmr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pmmr

Every month we try and update this database with for pmmr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pmmr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.