Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Capecitabine

Vaccines

Immunomodulating Agents

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

XH001

a type of immunotherapy that targets CTLA-4 protein on T cells

Ipilimumab Injection

Chemotherapy

Wenming WU, Prof.

This is a single-center, open label, single-arm, investigator-initiated study to evaluate the efficacy and safety of XH001 (neoantigen cancer vaccine) sequential combination with ipilimumab and chemotherapy in pancreatic cancer patients following surgical resection.

XH001 Combination With Ipilimumab and Chemotherapy for Patients With Resected Pancreatic Cancer

Efficacy and Safety Trial of XH001 (Neoantigen Cancer Vaccine) Sequential Combination With Ipilimumab and Chemotherapy for Patients With Resected Pancreatic Cancer

Antigen-specific T-cell responses in peripheral blood

Incidence and severity of adverse events (AEs), clinically significant abnormal changes in laboratory tests and other investigations (based on the Criteria for the Evaluation of Adverse Events \[CTCAE\] v5.0).

NeoCura

Wu Wenming

Prof.

Symptoms and General Pathology

Carcinoma

Neoplasm Metastasis

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Liver Diseases

Neoplastic Processes

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Standard treatment of HCC by the combination atezolizumab-bevacizumab, 1 cure each 3 weeks during 24 months

Standard treatment of HCC by the combination atezolizumab-bevacizumab with addition of ipilimumab for the 4 firsts cures of treatment each 3 weeks, then only treatment by the doublet atezolizumab-bevacizumab each 3 weeks. The total duration of treatment is 24 months.

Administration of a combine treatment by atezolizumab and bevacizumab, with addition of ipilimumab for patients enrolled in the experimental arm

One of the standard treatment's product for HCC management

Atezolizumab Injection

Meriem Guarssifi

Marie Moreau

Hélène Regnault, Gastroentérologue

Sylvain MANFREDI, Hépato-gastroentérologue

Maryline DEBETTE-GRATIEN

Philippe MERLE, Hépatologue

Anne Claire FRIN, Gastroentérologue

Manon ALLAIRE, Gastroentérologue

Marie LEQUOY

Gastroentérologue

Jean-Frédérique BLANC, Gastroentérologue

TRIPLET HCC is a phase II-III trial that assess the effectivness of addition of ipilimumab to the combination atezolizumab-bevacizumab, on global survival and response to the treatment, for patients with advanced or metastatic hepatocellular carcinoma. The theoretical duration of the study is 5 years. In the scope of this study, each patient will have 2 years of treatment and 2 years of follow-up from their enrollment date.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and ranks fourth in terms of cancer-related mortality worldwide . Unfortunately, the diagnosis of HCC is often made late in the cure of the disease when the tumour has spread outside the liver parenchyma as portal vein invasion or distant metastases. In the history of HCC patients, a significant proportion will sooner or later face systemic therapies as they are no longer eligible for radical or locoregional therapies. Cytotoxic chemotherapy and hormonal therapies have never shown significant benefit on overall survival (OS) . The first systemic therapy to show a significant beneficial impact on HCC outcome was the tyrosine kinase inhibitor (TKI) sorafenib, an anti-angiogenic agent (AAA) with anti-proliferative properties on HCC . For nearly a decade, all systemic therapies tested in randomised controlled trials as first-line systemic therapy (1L) head-to-head with sorafenib, or as 2L after sorafenib failure have not shown significant benefit. In 2018, Kudo et al. showed that lenvatinib, another TKI with anti-angiogenic properties, was at least equivalent to sorafenib in 1L in the REFLECT non-inferiority trial \[5\]. Other AAA TKIs with anti-cancer properties on HCC cells have demonstrated efficacy in 2L: regorafenib after progression on sorafenib in 2017 , and cabozantinib after progression on or intolerance to sorafenib in 2018 . In addition, ramucirumab, a monoclonal antibody targeting VEGFR-2, has shown significant benefit in a specific subpopulation of HCC patients with high baseline alpha-fetoprotein levels ≥ 400 ng/ml . However, all these options were strictly palliative with no long-term survivors and lack of potential recovery. Immuno-oncology (IO) approaches have completely revolutionised the paradigm of systemic HCC therapies with nonetheless a significant increase in median OS in IO-based combination strategies, but also the emergence of the possibility of long-term survivors and, for some patients, hope for a complete response and possibly a final cure.

Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab in Patients With Hepatocellular Carcinoma Receiving First-line Systemic Therapy

Randomised, Open-label, Phase II-III Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab in Patients With Hepatocellular Carcinoma Receiving First-line Systemic Therapy

Assess the percentage of patients with an objective response (complete response or partial response) according to the investigator (RECIST v1.1) for both treatments arms,

The overall survival is defined as the time to death (whatever the cause) or date of last news

Progression is based on CT-Scan and only radiological progression have to be taking into account. Progression-free survival is defined as the time from randomization to radiological progression or death. Patients alive without progression will be censored at date of last news.

Assess the percentage of patients with an objective response (complete response or partial response) according to the investigator (RECIST v1.1) for both treatments

Federation Francophone de Cancerologie Digestive

Respiratory Tract (Lung and Bronchial) Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Nivolumab

Receive preoperative nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).

Receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).

Nivolumab Injection

Patrick Forde, MD

The proposed study will evaluate the safety and feasibility of neoadjuvant nivolumab +/- ipilimumab in resectable MPM. In addition, maintenance nivolumab will be administered for 1 year following completion of standard bi-/tri-modality therapy.

For Arm A 15 patients with resectable MPM will be enrolled and receive preoperative nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).

Subsequent to full accrual to Arm A, 15 patients with resectable MPM will be enrolled and receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).

Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma

Number of participants with grade III/IV adverse events defined by CTCAE v5.0, occurring within 100 days of last study drug administration or 30 days post-surgery (whichever is longer).

Feasibility as measured by the number of participants who complete of neoadjuvant treatment with nivolumab +/- ipilimumab and proceed to surgery without extended treatment-related delay (\>24 days from preplanned surgery date).

Number of participants with pathologic response, defined as ≤10% residual viable tumor cells in the resection specimen, and pathologic complete response (no residual viable tumor cells in the resection specimen).

Number of participants with radiographic response as determined utilizing RECIST 1.1, modified RECIST for pleural tumors, and change in FDG avidity on PET/CT pre- and post-treatment.

Toxicity as assessed by number of participants experienced grade III/IV adverse events as defined by CTCAE v5.0 within 100 days of last study drug administration

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
XH001 Combination With Ipilimumab and Chemotherapy for Patients With Resected Pancreatic Cancer	NCT06353646	Pancreatic Canc...	XH001 Ipilimumab Inje... Chemotherapy	18 Years - 75 Years	Peking Union Medical College Hospital
Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab in Patients With Hepatocellular Carcinoma Receiving First-line Systemic Therapy	NCT05665348	HCC - Hepatocel... Metastatic Canc... Metastatic Tumo...	Ipilimumab Inje... Atezolizumab In... Bevacizumab	18 Years -	Federation Francophone de Cancerologie Digestive
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma	NCT03918252	Mesothelioma	Nivolumab Injec... Ipilimumab Inje...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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