Symptoms and General Pathology

Wounds and Injuries

All Conditions

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Hyperthermia

Fever

Body Temperature Changes

Stress Disorders, Traumatic

Heat Stress Disorders

Hyperthermal treatment one or three times per week for 60 minutes

Hyperthermal treatment

Hyperthermia - a warming of the tumor at 42-43 ° C - in combination with radiation and / or chemotherapy is a proven method of treatment for malignant tumors. The amplification of the effect of radiotherapy and various chemotherapeutic agents (platinum analogues, nitrogen-Lost derivatives, cytotoxic antibiotics) is experimentally demonstrated. Randomized clinical trials have shown a better chance of survival and better local tumor control without increasing the toxicity of combined treatment especially also in children's tumors. The combination of hyperthermia and radiation therapy is more effective than radiotherapy alone. Hyperthermal temperatures increase blood circulation in tumors as a response to stimulation with heat. Tumor tissue, having a minor circulation and being acidotic, is resistant to radiotherapy, but sensitive to hyperthermia, while tumor with a high blood flow is sensitivity to radiation. This positive interaction is a compelling reason for the combination of hyperthermia and ionized radiation.

Hyperthermia, in combination with chemotherapy, increases the concentration of cytostatics in the tumor region, raising blood flow caused by warmth. In addition, hyperthermia increases toxicity of drugs in cells, being normally resistant to many drugs. Hyperthermia can synergistically be combined with chemotherapy treating "high risk" - tumors with curative intention.

In addition to the clinical use of surface hyperthermia (BSD 500 - O), with appropriate treatment of tumors up to 3 cm deep from the surface of the body with established indications and palliative indication in advanced stages of cancer, a prospective, randomized study with quality-controlled thermometry shall establish the optimal sequence of Hyperthermia in combination with irradiation. Therefore the treatment sequence of once per weeks is compared to a sequence of three times per week.

Optimal Application Dose of Superficial Hyperthermia

Phase III Study for Analysis of the Optimal Application Dose of Superficial Hyperthermia

Universitätsmedizin Mannheim

Prof. Dr. med. Wenz

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Infections

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Neoplasm Metastasis

Breast Neoplasms

Triple Negative Breast Neoplasms

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Virus Diseases

Vaccinia

Carcinoma, Merkel Cell

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Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

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Skin Neoplasms

Skin Diseases

Neoplasms, Connective and Soft Tissue

Breast Diseases

Neoplastic Processes

Communicable Diseases

Polyomavirus Infections

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Carcinoma, Neuroendocrine

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Neoplasms, Glandular and Epithelial

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Neuroendocrine Tumor

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All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Pembrolizumab

Immunoglobulins

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Dose escalation with repeated administrations of BT-001 directly into tumor as a single agent, in patients with metastatic or advanced solid tumors.

Repeated administrations of BT-001 directly into tumor in combination with infusions of pembrolizumab in patients with metastatic or advanced soft tissue sarcoma (STS), Merkel cell carcinoma (MCC), melanoma, triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC)..

Repeated administrations of BT-001 directly into tumor in combination with infusions of pembrolizumab in several cohorts of patients with defined metastatic or advanced solid tumor conditions: soft tissue sarcoma, Merkel cell carcinoma, melanoma, triple negative breast cancer, non-small cell lung cancer.

Oncolytic Vaccinia virus containing genes encoding the 4-E03 human recombinant anti-hCTLA4 antibody and human GM-CSF administered at different dose \[Phase I, Part A\]; one dose lower and at Recommended Dose for Part B \[Phase I, Part B\] by intra-tumoral (IT) route.

BT-001

Programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.

Pembrolizumab [KEYTRUDA®]

Transgene EU, Clinical Operations Department

Pr Baurain

Pr Italiano

Dr Cassier

Pr Lebbé

Dr Champiat

This is a Phase I/IIa, multicenter, open-label, consecutive cohorts, dose-escalation study of BT-001 with repeated IT administrations alone and in combination with IV infusions of pembrolizumab.

This study will include 3 parts:

* Phase I, Part A: Repeated intra-tumoral (IT) administrations of BT-001 as a single agent, in patients with metastatic/advanced solid tumors; dose-escalation will be employed.
* Phase I, Part B: Repeated IT administrations of BT-001 in combination with intravenous (IV) infusions of pembrolizumab in patients with metastatic/advanced soft tissue sarcoma (STS), Merkel cell carcinoma (MCC), melanoma, triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC)..
* Phase IIa: Repeated IT administrations of BT-001 in combination with IV infusions of pembrolizumab in several cohorts of patients with defined metastatic or advanced solid tumor conditions.

A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors

A Phase I/IIa Study of Intra-tumoral BT-001 (TG6030) Administered Alone and in Combination With Pembrolizumab in Patients With Cutaneous or, Subcutaneous Lesions or Easily Injectable Lymph Nodes of Metastatic/Advanced Solid Tumors.

Incidence of Adverse Event reported per NCI-CTCAE v5.0, Dose limiting toxicity and Serious Adverse Events.

RDPB based on the safety data collected during the dose escalation phase (Phase I, Part A).

Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria over the the total number of evaluable patients. for injected and non-injected lesion(s)

Percentage of patients whose best overall response is either a Complete Response, a Partial Response or Stable Disease according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria over the the total number of evaluable patients.

Percentage of patients whose best overall response is either a Complete Response, a Partial Response or Stable Disease according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria or immune RECIST over the total number of evaluable patients.

Time from the first BT-001 administration to the date of first documented tumor progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria or immune RECIST or death due to any cause, whichever occurs first over evaluable patients

Time from the date of first documented response (CR or PR) to the date of first documented disease progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria or immune RECIST or the date of death due to underlying cancer over the number of patients whose Best Overall Response is Complete Response or Partial Response.

Time from first BT-001 administration to the date of death due to any cause over evalauable patients.

BioInvent International AB

Merck Sharp & Dohme LLC

Transgene

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Optimal Application Dose of Superficial Hyperthermia	NCT00766233	Tumors	Hyperthermal tr...	18 Years -	Universitätsmedizin Mannheim
A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors	NCT04725331	Metastatic Canc... Soft Tissue Sar... Merkel Cell Car... Melanoma Triple Negative... Non Small Cell ...	BT-001 Pembrolizumab [...	18 Years -	Transgene
Optimal Application Dose of Superficial Hyperthermia	NCT00766233	Tumors	Hyperthermal tr...	18 Years -	Universitätsmedizin Mannheim

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