Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Pertuzumab

Bevacizumab

Atezolizumab

Immunomodulating Agents

Ipatasertib

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

atezolizumab alone, administered as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.

atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.

trastuzumab + pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.

atezolizumab as one single IV infusion in combination with trastuzumab + pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.

Patients randomized to an atezolizumab arm will receive atezolizumab 840 mg IV on D1 (15 days +/- 48 h before the surgery date or the biopsy prior to the start of standard of care neoadjuvant systemic treatment.).

Atezolizumab Injection

Patients in the atezolizumab plus bevacizumab arm will receive a unique dose of bevacizumab as 10 mg/kg administered by IV infusion over 60 mins on day 1 cycle 1 (15 days before surgery +/- 48 h), the same day as atezolizumab.

Patients in the atezolizumab plus trastuzumab plus pertuzumab arm will receive single doses of pertuzumab on day 1 administered IV. Pertuzumab will be administered IV at a loading dose of 840 mg.

Patients in the atezolizumab plus trastuzumab plus pertuzumab arm will receive single doses of Trastuzumab on day 1 administered IV. Trastuzumab will be given at a loading dose of 8 mg/kg.

Joana Mourato Ribeiro, Dr

The aim of this study is to determine, using immunohistochemistry (IHC) on biopsies and surgically removed tumor if short-treatment immunotherapy with atezolizumab monotherapy or in combination with other biologic agents (ipatasertib / Bevacizumab / Trastuzumab / Pertuzumab) is associated with increased levels of activated GzmB+ CD8+ T cells from baseline to post treatment sample.

Moreover, from baseline to post treatment sample, evolution of others biomarkers will be studied : GzmB/CD8, CD8/FoxP3, CD8/CD68 in IHC, cell proliferation, PD-L1, MHC-I, change in gene expression (RNA-Seq). Tjis study aim also to assess the safety and tolerability of study treatments in this population and to determine the effect of short-term immunotherapy treatment in pCR at surgery.

Patients will undergo tumor biopsies at screening and 15 days after the beginning of treatment (if they start neoadjuvant chemotherapy) / at surgery, in order to evaluate in IHC evolution of activated GzmB+ CD8+ T cells and evaluate other markers

It targets 2 different cohorts: newly diagnosed, non-metastatic early-stage triple-negative (TNBC) or HER2+ breast cancer. TNBC cohort is composed of 2 open-label, randomized arms, HER2+ of 2 arms.

A maximum of 185 patients will be included in the trial

Tumor evaluation will be performed by clinical examination and Breast echography at baseline and end of treatment visit.

The safety of the product will be assessed at each cycle, through complete clinical exams, biological tests and through the collection of ongoing toxicities or adverse events.

Cohort 1 In TNBC patients t will be composed of 4 open-label, randomized arms:

Arm 1A: atezolizumab alone, administered as one single IV infusion on day -15 +/- 48 h Arm 1B: atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.

Cohort 2 in HER2-positive patients will be composed of 2 arms:

Arm 2A: pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.

Arm 2B: atezolizumab as one single IV infusion in combination with trastuzumab + pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.

The design of this study follows an adaptive, open, prospective randomized model : Cohort 1 TNBC patients: they will be randomized 1:1 to either atezolizumab alone administered as one single IV infusion on day -15 +/- 48h prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment, or atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48h prior to the date of surgery or the start of neoadjuvant treatment Cohort 2 in HER2-positive patients: they will be randomized 1:1 to either trastuzumab and pertuzumab for one IV infusion on day -15 +/- 48h prior to the surgery or the start of neoadjuvant treatment, or atezolizumab as one single IV infusion in combination with trastuzumab and pertuzumab for one IV infusion on day -15 +/- 48h prior to the surgery or the start of neoadjuvant treatment

Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy

To determine, using immunohistochemistry (IHC) on biopsies and surgically removed tumor whether short-treatment immunotherapy with atezolizumab monotherapy or in combination with other biologic agents is associated with increased levels of activated GzmB+ CD8+ T cells from baseline to post treatment sample.

Clinical response after experimental therapy, defined as a \> 30% decrease in tumour diameter from baseline breast ultrasound based on investigator assessment

pCR defined as the absence of any residual invasive cancer based on histological evaluation of the resected specimen during definitive breast cancer surgery.

Changes in CD8+ expression from baseline (pre-study) to end of study-treatment biopsies

Changes in PD-L1 expression from baseline (pre-study) to end of study-treatment biopsies

Changes in % of Ki67 from baseline (pre-study) to end of study-treatment biopsies

Changes from baseline tumour tissue to end of treatment in immune infiltrates.

Changes from baseline tumour tissue to end of treatment in immune-related gene expression

Hoffmann-La Roche

Gustave Roussy, Cancer Campus, Grand Paris

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Neoplasm Metastasis

Carcinoma

Carcinoma, Squamous Cell

Esophageal Neoplasms

Recurrence

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

cabozantinib 40mg PO QD atezolizumab 1200mg IVD 30-60mins Q3W

Cabozantinib 40 MG

atezolizumab (Tecentriq) 1200mg IVF 30-60mins Q3W

Hung-Yang Kuo, M.D.

Min-Yi Cheng

Daniel Fu-Chang Tsai, M.D.,Ph.D.

Chih-Hung Hsu, M.D.,Ph.D.

Ta-Chen Huang, M.D.

Jhe-Cyuan Guo, M.D.

Chia-Chi Lin, M.D.,Ph.D.

Kun-Huei Yeh, M.D.,Ph.D.

Jang-Ming Lee, M.D.,Ph.D.

Pei-Ming Huang, M.D.,Ph.D.

To demonstrate that combination of cabozantinib and atezolizumab is safe and efficacious in patients with recurrent/metastatic esophageal squamous cell carcinoma.

Patients with histologically proven squamous cell carcinoma of esophagus and had progression from first-line platinum-based chemotherapy for recurrent or metastatic ESCC, or progression within 6 months after neoadjuvant, definitive, or adjuvant chemo(radio) -therapy for loco-regional ESCC would be eligible for this trial. Eligible patients will receive daily 40mg cabozantinib plus i.v. atezolizumab 1200mg Q3W for treatment response evaluation. Primary endpoint is the objective response rate, and secondary endpoints include progression-free survival, overall survival, and safety profiles.

Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

A Single-arm Phase II Study of Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma Who Failed a Platinum-based Chemotherapy

Overall response rate (ORR) is the proportion of patients whose tumor is significantly reduced.

Progression-free survival (PFS) is the time from enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) and will be conducted in the whole study population. It is designed to include progression events as determined by the investigators per RECIST 1.1 or death.

Overall survival (OS) is the time from enrollment to death of any cause or the last follow-up (censored).

The incidence and severity of toxicity will be summarized according to the NCI Common Toxicity Criteria Version 4.0.

Ipsen

Roche Pharma AG

National Taiwan University Hospital

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Liver Diseases

Herbal and Botanical

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Chlorotrianisene

Immunoglobulins, Intravenous

Cola

THIS IS A SINGLE ARM PILOT/FEASABILITY STUDY. THE STUDY CONSISTS OF A SCREENING PERIOD (DAY -28 TO DAY -1), A TREATMENT PERIOD, AND A TREATMENT DISCONTINUATION VISIT.

The atezolizumab and bevacizumab combination will be given every 21 days, atezolizumab 1200 mg and bevacizumab 15 mg/kg will be administered intravenously on a Q3 week schedule.

Subjects will start the combination of bevacizumab and atezolizumab followed by TACE treatment 4 weeks ±1 week or up to 5 weeks after study drugs. Full recovery from the procedure is required prior to systemic treatment.

Atezolizumab is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular carcinoma, and alveolar soft part sarcoma It is a fully humanized, engineered monoclonal antibody of Immunoglobulin G1 (IgG1) isotype against the protein programmed cell death-ligand 1 (PD-L1).

Bevacizumab, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

Transarterial chemoembolization (TACE) is a local therapy for HCC which induces tumor necrosis.

Transarterial chemoembolization

Cynthia Voghell

Maxime Oriol

Stacy Stein, MD

There is an unmet need for patients with intermediate stage hepatocellular carcinoma (HCC). It is known that local tumor ablation can increase tumor immunogenicity by releasing tumor associated antigens, potentially increasing the response to immune therapy not just locally, but systemically. In addition, there is now positive data with immune therapy in advanced HCC, there is renewed interest in the combination of local therapy and systemic therapy in Barcelona Clinic Liver Clinic B (BCLC B) patients with systemic therapies other than sorafenib. Based on this data, the investigators plan to examine the atezolizumab and bevacizumab combination with Transarterial Chemoembolization (TACE) in patients with BCLC B HCC.

Targeting the Programmed Death-Ligand 1 (PD-L1) pathway with atezolizumab has demonstrated activity in patients with advanced malignancies who have failed standard-of-care therapies. Objective responses have been observed across a broad range of malignancies, including Non-Small-Cell Lung Cancer (NSCLC), urothelial carcinoma, Renal Cell Carcinoma (RCC), melanoma, colorectal cancer, head and neck cancer, gastric cancer, breast cancer, and sarcoma (see Atezolizumab Investigator's Brochure for detailed efficacy results).

Atezolizumab has been generally well tolerated. Adverse events with potentially immune-related causes consistent with an immunotherapeutic agent, including rash, influenza-like illness endocrinopathies, hepatitis or transaminitis, pneumonitis colitis, and myasthenia gravis, have been observed (see Atezolizumab Investigator's Brochure for detailed safety results). To date, these events have been manageable with treatment or interruption of atezolizumab treatment.

The combination of atezolizumab and bevacizumab in HCC has been well studied in both the phase 1 G030140 study and the phase 3 IMBrave150 study with response rates of 36% and 27% respectively. A phase 2 study of bevacizumab and TACE showed that the combination can be safely administered on the same day. Given concern for risk of bleeding with bevacizumab, all patients on these two studies had recent Endoscopic Gastroduodenoscopies (EGDs) and no patients with untreated varices were included. The risk of bleeding on both studies were reported as low, and risk of benefit was presented as outweighing risk.

This trial will enroll patients with HCC who have BCLC B disease and are not candidates for curative treatment but are candidates for TACE. Typically, these patients would be treated with local treatment alone, but given the relatively poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates. The benefit-risk ratio for atezolizumab and bevacizumab in combination with TACE is expected to be acceptable in this setting.

This is an open-label, single-arm study which will be performed to examine the safety and tolerability of the combination of atezolizumab and bevacizumab with TACE for patients with BCLC B HCC.

Atezolizumab and Bevacizumab in Combination With TACE for Patients With BCLC B HCC

Safety and tolerability will be assessed by the rate of grade 3 or higher Adverse Events (AEs), graded using the CTCAE version 5. The rate will be assessed using the Bayesian Predictive Probability approach.

Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) will be used to assess overall response rate.

Response Evaluation Criteria in Hepatocellular Carcinoma-Specific Modified RECIST (HCC mRECIST) will be used to assess overall response rate.

Defined as the time from trial enrollment until objective tumor progression by RECIST, Response Evaluation Criteria in Solid Tumors criteria.

Defined as the interval of time from the day of the images after a TACE procedure to the time or progression, new vascular invasion or extrahepatic spread also is counted as progression.

Defined as time to untreatable tumor progression and/or transient deterioration to Child-Pugh C score and/or appearance of vascular invasion/extrahepatic spread. Child-Pugh score ranges from 5-15. Child-Pugh C = 10-15. A higher score indicates a worse outcome.

Genentech, Inc.

Yale University

Neoplastic Processes

Ipilimumab

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

Ipilimumab Injection

One of the standard treatment's product for HCC management

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy	NCT05180006	Breast Cancer	Atezolizumab In... Bevacizumab Pertuzumab Trastuzumab	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma	NCT05007613	Esophageal Canc... Metastatic Canc... Squamous Cell C...	Cabozantinib 40... Atezolizumab In...	20 Years -	National Taiwan University Hospital
Atezolizumab and Bevacizumab in Combination With TACE for Patients With BCLC B HCC	NCT05776875	Hepatocellular ... BCLC Stage B He...	Atezolizumab In... Bevacizumab Transarterial c...	18 Years -	Yale University
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
Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma	NCT05007613	Esophageal Canc... Metastatic Canc... Squamous Cell C...	Cabozantinib 40... Atezolizumab In...	20 Years -	National Taiwan University Hospital
Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy	NCT05180006	Breast Cancer	Atezolizumab In... Bevacizumab Pertuzumab Trastuzumab	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for atezolizumab injection