Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Peritoneal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Vasoconstrictor Agents

Respiratory System Agents

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Gastrointestinal Agents

Epinephrine

Avelumab

Liver Extracts

Pancrelipase

Racepinephrine

Epinephryl borate

Pancreatin

Antineoplastic Agents, Immunological

Biweekly intra-tumoral injections of escalating doses (6 mg, 12 mg, 24 mg and 30 mg) of IMP321 as a monotherapy (intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal gland, pancreas) are not allowed)

Biweekly intra-peritoneal, escalating doses of IMP321 (1 mg, 3 mg, 6 mg, 12 mg and 30 mg)

Subcutaneous (s.c.) injections with the optimal dose of IMP321 defined in the AIPAC trial for a maximum of 24 weeks

Avelumab and IMP321 as follows:

* 800 mg avelumab every 2 weeks i.v. (for a maximum of 24 cycles \[48 weeks\])
* 6 mg (cohort 1) or 30 mg (cohort 2) IMP321 every 2 weeks s.c. (for a maximum of 12 cycles \[24 weeks\])

Avelumab and IMP321 as follows:

• 800 mg avelumab every 2 weeks i.v. and 30 mg IMP321 every 2 weeks s.c. for a maximum of 24 cycles \[12 months\]

LAG-3Ig fusion protein, highly potent activator of antigen presenting cells

IMP321

Salah-Eddin Al-Batran, MD

Sabine Beck, PhD

Thorsten O. Götze, Prof. Dr.

Thorsten O. Götze, MD

Thorsten Götze, MD

This phase I trial aims to investigate a potential enhancement of IMP321 immune-activating effects by new routes of administration: direct injection of IMP321 into the tumor tissue; intra-peritoneal therapy; combination of chemotherapy and/or immunotherapy/targeted therapy with active immunotherapy

Up to now, IMP321 is solely administered by sub-cutaneous injection (e.g. on the anterior face of the thigh). In this study, we investigate whether a direct injection of IMP321 into the tumor tissue will be a useful option to improve anti-tumor immune response by placing the immune-therapeutic agent in direct vicinity of immune infiltrates in the tumor bed. This bypasses processes necessary for drug delivery to cells of solid tumors following systemic administration, like transport within vessels, transport across vasculature walls into surrounding tissues, and - in cases of peritoneal metastases - transport through the interstitial space within a tumor. For the latter case, we will also explore if an intra-peritoneal therapy represents a feasible alternative by means of delivering high drug concentrations directly to tumors located in the peritoneal cavity.

Furthermore, we will explore the possibility to extend the positive results obtained by subcutaneous injections of IMP321 in metastatic renal cell and breast carcinomas to further solid tumor entities. In this part of the study, patients will be treated with the standard-of-care (SOC) chemotherapy and/or immunotherapy/targeted therapy for their tumor entity along with subcutaneous injections of IMP321.

Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors

An Explorative, Open-labeled, Phase I Study to Evaluate the Feasibility and the Safety of IMP321 in Combination With Immunotherapeutic/Targeted/Chemotherapeutic Agents or Via New Routes of Application in Advanced Stage Solid Tumors

Rate of patients receiving the protocol treatment without occurrence of a dose limiting toxicity

Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

Objective response rate according to RECIST 1.1 and endoscopic response criteria

PFS will be measured as time from inclusion until disease progression or death of any cause

OS will be measured as time from inclusion to death of any cause

Peripheral blood monocyte number and CD8 T-cell number, associated activation markers, tumor-infiltrating immune cells

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Vaccines

Immunomodulating Agents

Monatide (IMS 3015)

Immunologic Factors

Adjuvants, Immunologic

9 patients initially planned: patients received peptides with IMP321/LAG-3Ig and Montanide in 2 injections sites at 5 cm distance from each other 2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide)

Groupe2: 2 vaccine injections in different limb should include 9 patients that were initially planned: patients received the same vaccine in 2 syringes injected each in a distinct limb (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide)

Groupe3: 2 vaccine injections in distinct limb should include 9 patients that were initially planned; due to premature trial termination, no patients could be enrolled. Patients of this group should have received the same vaccine but without the MHC class II peptide (MAGE-A3)

Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other.

2 vaccine injections in 1 limb

Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs.

2 vaccine injections in distinct limbs

2 "vaccine injections" in distinct limbs

Olivier Michielin, MD PhD

The purpose of this study is to determine whether vaccination with tumor antigenic peptides and both IMP321/LAG-3 and Montanide adjuvants can induce an immune response in melanoma patients and to assess the safety and tolerability of this vaccination. Tumor responses following this vaccination will also be documented.

The primary objective of this study is:

* to evaluate melanoma antigen specific immune response induced by this vaccination with tumor antigenic peptides derived from MAGE-A3 (Melanoma Antigen family A3) (MHCI: MAGE-A3.A2 and MHCII: MAGE-A3.DP4), NY-ESO-1 (New York Esophageal squamous cell carcinoma antigen-1), Melan A (analog ELA and native EAA) and NA-17A with IMP321 (ImmuFact)/ LAG-3Ig (Lymphocyte activation gene-3 immunoglobulin-like domains) as adjuvant/immunostimulant, formulated with Montanide ISA-51.
* to assess the safety and tolerability of this vaccination

The secondary objective is to document tumor responses in patients following this vaccination.

open label, non comparative study in patients suffering from stage II, III or IV melanoma

Immunotherapy of HLA-A2 Positive Stage II-IV Melanoma Patients

Vaccination of Melanoma Patients (Stage II-IV) With ImmuFact IMP321, Tumor Antigenic Peptides and Montanide

Cellular immunity was evaluated through the activation and the expansion of Melan-A-specific CD8+ cytotoxic T lymphocytes. Their frequency was measured in the peripheral blood mononuclear cells (PBMC) directly ex vivo (i.e. without prior in vitro expansion) by multicolor flow cytometry with Melan-A ELA tetramers.

The fold change for each time point compared to baseline was calculated as: Melan-A-specific CD8+ T cell frequency at the time point/ Melan-A-specific CD8+ T cell frequency at baseline.

Significant T cell response is defined by at least 2-fold change of Melan-A-specific CD8+ T cell frequency as compared to pre-immunotherapy.

The activation of peptide-specific CD4+ T cells was analyzed in vitro before and after vaccination by Intracellular Cytokine Staining (ICS).

From each patient, total CD4+ T-cells were stimulated in the presence of peptide MAGE-A3.DP4 LP (MAGE-A3243-258 peptide presented by autologous cells).

After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged.

Specific CD4+ T cells responses were identified via detection of IFN-γ producing cells.

The activation of peptide-specific CD4+ T cells was analyzed in vitro before and after vaccination by ICS.

From each patient, total CD4+ T-cells were stimulated in the presence of peptide MAGE-A3.DP4 LP (MAGE-A3243-258 peptide presented by autologous cells).

After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged.

Specific CD4+ T cells responses were identified via detection of TNF-α producing cells.

Frequencies of specific MAGE-A3.DP4-specific CD4+ T cells were quantified by flow cytometry using class II tetramers after 10 days of in vitro stimulation.

The fold change for each time point compared to baseline was calculated as: MAGE-A3.DP4-specific CD4+ T cell frequency at the time point/ MAGE-A3.DP4-specific CD4+ T cell frequency at baseline.

After 12 days of in vitro stimulation with Melan-A peptides, CD8+ T cells were analyzed by flow cytometry using tetramer staining.

The fold change for each time point compared to baseline was calculated as: Melan-A-specific CD8+ T cell frequency at the time point/ Melan-A-specific CD8+ T cell frequency at baseline.

Significant T cell response is defined by at least 2-fold change of Melan-A-specific CD8+ T cell frequency as compared to pre-immunotherapy.

After 12 days of in vitro stimulation with NY-ESO-1 peptide, CD8+ T cells were analyzed by flow cytometry using tetramer staining.

The fold change for each time point compared to baseline was calculated as: NY-ESO-1-specific CD8+ T cell frequency at the time point/ NY-ESO-1-specific CD8+ T cell frequency at baseline.

The assessment of the baseline disease status was performed, using CT (Computed Tomography) scan or PET (Positron Emission Tomography)/ CT scan, at screening visit or within 8 weeks preceding the screening visit. Imagery examinations occurred after the end of each vaccination cycle. The tumor response was assessed according to the classification World Health Organization (WHO) 1979 and defined as:

* No evidence of disease (NED),
* Stable disease (SD): change in size of all measurable lesions (the sum of the products of the greatest and perpendicular parameters), of less than a 25% increase or 25% decrease from baseline for at least 4 weeks, without appearance of new lesions or progression of any lesion.
* Progressive disease (PD): appearance of new tumors, or increase in size of any measurable tumor by at least 25% of the sum of the product of the greatest and perpendicular diameter.

Immutep S.A.S.

Centre Hospitalier Universitaire Vaudois

Professor

No patients were included in the group 3. All adverse events were collected irrespective of their frequency, their severity and relationship to the study drug.

The adverse events that were expected, according to the Investigator's Brochure of the different vaccine components, were assessed systematically at each visit study.

2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide)

2 vaccine injections in 1 limb: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other.

Group 1

2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide)

2 vaccine injections in different limbs: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs.

Group 2

2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A peptide + IMP321 + Montanide)

2 vaccine injections in different limbs, the vaccine does not contain the MHC class II peptide MAGE-A3-DP4: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A peptide with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in different limbs.

Group 3

9 patients initially planned: patients received peptides with IMP321/LAG-3Ig and Montanide in 2 injections sites at 5 cm distance from each other 2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide)(vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide)

2 vaccine injections in 1 limb: Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other.

Group 1: 2 Vaccine Injections in 1 Limb

9 patients initially planned: patients received the same vaccine in 2 syringes injected each in a distinct limb 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide)

2 vaccine injections in different limbs: Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs.

Group 2: 2 Injections in Different Limbs

9 patients initially planned: due to premature trial termination, no patients could be enrolled in this last group. 2 vaccine injections in different limbs; patients of this group should have received the same vaccine but without the MHC class II peptide (MAGE-A3 LP) in 2 syringes injected each in a distinct limb.

2 vaccine injections without MHC class II peptide in different limbs: Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A peptide with IMP321/LAG-3 ± Montanide.

Group 3: 2 Injections in Different Limbs

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Switzerland

Region of Enrollment

Due to premature trial termination, no patients could be enrolled in the Group 3.

Early termination leading to small numbers of subjects analyzed

Prof. Olivier Michielin, MD PhD

End cycle 1

End cycle 2

End cycle 3

Follow up

Ex Vivo Frequency of Melan-A Specific CD8+T Cells

Baseline

End of cycle 1

End of cycle 2

End of cycle 3

In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Interferon-gamma (IFN-γ)

In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Tumor Necrosis Factor-alpha (TNF-α)

In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells

In Vitro Frequency of Melan-A-specific CD8+T Cells After Stimulation

In Vitro Frequency of NY-ESO-1-specific CD8+ T Cells

Disease status at cycle 1 end

Disease status at cycle 2 end

Disease status at cycle 3 end

Tumor Response

Cycle 1

Cycle 2

Cycle 3

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Renal Cell

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

subcutaneous injections of IMP321 every 14 days for three months (6 injections. Doses tested: 50, 250, 1,250, 6,250 or 30,000 µg

Bernard Escudier, M.D

Single-center, open label, non-randomized, fixed dose-escalation, phase 1 study, performed in ambulatory and day-hospital setting

This is a single-center, single-arm, open label, non-randomized, fixed dose-escalation, phase 1 study, performed in ambulatory and day-hospital setting. After a screening period, patients will enter a drug administration period, followed by a 'post-study' period.

Four IMP321 dose levels, 50 µg, 250 µg, 1.250 mg, 6.250 mg and 30 mg will be evaluated in successive cohorts of patients. At any given dose level 3 patients will be administered one subcutaneous dose every 2 weeks for a total of 12 weeks (6 injections in total), separated by 13-day administration-free intervals.

The next (higher) dose level will be dosed to 3 new patients if the previous dose level has been well tolerated. Investigator will decide whether the safety is acceptable by performing an evaluation after the third administration (at week 8) and if the next patients can be included.

The successive cohorts of patients are summarized as follows:

* Cohort A will correspond to a group of 3 patients receiving the 50 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort B will correspond to a group of 3 patients receiving the 250 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort C will correspond to a group of 3 patients receiving the 1,250 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort D will correspond to a group of 3 patients receiving the 1,250 µg dose. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration, the following cohort will be undertaken.
* Cohort E will correspond to a group of 3 patients receiving the 6,250 µg dose. The patients will receive their first administration one-by-one with a two-weeks interval. If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration for the last patient, the following cohort will be undertaken.
* Cohort F will correspond to a group of 3 patients receiving the 6,250 µg dose. If the tolerability of this dose level has been judged acceptable in cohort E, the three patients will receive their first IMP321 injection simultaneously.
* Cohort G will correspond to a group of 3 patients receiving the 30,000 µg dose. The patients will receive their first IMP321 administration one-by-one with a two-weeks interval (+/- 5 days). If safety at this dose level is acceptable as evaluated a fortnight after the 6-week administration for the last patient, the following cohort will be undertaken.
* Cohort H will correspond to a group of 3 patients receiving the 30,000 µg dose. If the tolerability of this dose level has been judged acceptable in cohort E, the three patients will receive their first IMP321 injection simultaneously.

Once the main period of study has been completed, namely two weeks after a cohort is completed, i.e. at week 14, all patients will undergo an ambulatory 'post-study' examination.

Patients of the Cohort B, C, E, F and G will participate in a pharmacokinetic (PK) study and all patients in a pharmacodynamic (PD) study involving additional blood samples.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors	NCT03252938	Solid Tumors Peritoneal Carc...	IMP321 Avelumab	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Immunotherapy of HLA-A2 Positive Stage II-IV Melanoma Patients	NCT01308294	Melanoma	2 vaccine injec... 2 vaccine injec... 2 "vaccine inje...	18 Years -	Centre Hospitalier Universitaire Vaudois
IMP321 Phase 1 Trial in Metastatic Renal Cell Carcinoma (MRCC)	NCT00351949	Stage IV Renal ...	IMP321	18 Years -	Immutep S.A.S.
Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors	NCT03252938	Solid Tumors Peritoneal Carc...	IMP321 Avelumab	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors	NCT03252938	Solid Tumors Peritoneal Carc...	IMP321 Avelumab	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
IMP321 Phase 1 Trial in Metastatic Renal Cell Carcinoma (MRCC)	NCT00351949	Stage IV Renal ...	IMP321	18 Years -	Immutep S.A.S.

Spots Global Cancer Trial Database for imp321

Every month we try and update this database with for imp321 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 imp321

Every month we try and update this database with for imp321 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 imp321 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.