Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Respiratory Tract Infections

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

MDK-703 will be administered in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.

MDK-703 will be administered in sequential ascending doses in combination with a checkpoint inhibitor until unacceptable toxicity, disease progression, or withdrawal of consent.

MDK-703 will be administered as specified under Arm description.

MDK-703

Checkpoint inhibitor will be administered as specified under Arm description.

Checkpoint Inhibitor, Immune

Joseph Leveque, MD

This is an open-label, dose escalation and dose expansion study of MDK-703 as a monotherapy and in combination with other cancer therapies in adult study participants with advanced or metastatic solid tumors.

This is a Phase 1/2, open-label, multicenter, dose escalation and dose expansion study evaluating MDK-703 in adult study participants with advanced or metastatic solid tumors. This study will initially commence with dose escalation to evaluate the safety/tolerability of MDK-703 as a monotherapy and in combination with other cancer therapies. Once the monotherapy and/or combination therapy maximum tolerated dose (MTD), optimal biological dose (OBD), and/or recommended dose (RD) has been determined, then dose expansion of MDK-703 may commence in select populations of interest. The study will also evaluate the anti-tumor activity and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of MDK-703 as a monotherapy and in combination with other cancer therapies.

Multiple ascending dose escalation followed by dose expansion.

A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors

A Phase 1/2, Open-Label, Multicenter Study of MDK-703 as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors (ORCHID-1)

Based on toxicities observed from time of first dose through first cycle of treatment

Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5.0

Based on assessment of radiographic imaging per RECIST version 1.1

Blood concentration of MDK-703 at various timepoints

Time to achieve maximum blood concentration of MDK-703

Medikine, Inc.

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Disease Progression

Lymphopenia

Breast Diseases

Skin Diseases

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Syndrome

Immunologic Deficiency Syndromes

the patients will receive Placebo before the 1st and during the 3rd CT cycle (N=6)

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and the placebo during the 3rd CT cycle (N=6)

patients will receive the placebo before the 1st CT cycle and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6)

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6).

Placebo before the 1st (D0, D7, D14)and during the 3rd CT cycle (D57, D64, D71)

placebo

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and the placebo during the 3rd CT cycle (D57, D64, D71)

interleukin 7

patients will receive the placebo before the 1st CT cycle (D0, D7, D14) and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)

Isabelle Ray Coquart

The purpose of the study is to evaluate the impact of an immunotherapy by IL-7 on CD4 lymphopenia, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients.

The primary objective is to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count.

This study is a phase II, randomised, double-blind, placebo-controlled, single-centre.

24 patients will be included in the study.

A key secondary objective is to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy.

Other secondary objectives are to assess the impact of CYT107 treatment on the following parameters:

* Overall incidence of side effects (any type any grade)
* Progression-free survival (PFS)
* Compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles).
* CD4 lymphopenia over the study period

Exploratory biological markers

A series of biomarkers analyses will be performed to evaluate if CYT107 treatment will:

* selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations)
* selectively improve the functional response of T cells, DC subsets and NK cells.
* is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels)
* enable to increase TCR diversity (analysis of combinatorial diversity).

Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients

A Randomised, Multicentric, Phase 2a Study Evaluating the Impact of an Immunotherapy by IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients

Evolution of CD4 count from Day 0 to Week 11 with repeated measures from D0 to W12 (D0, D21, D57, D78).

Time from randomisation to first evidence of progression or death of any cause.

Number of CT cycles, CT dose delays and/or reduction, CT discontinuation

Evolution of CD4 count from Day 0 to end of study visit

Measure of frequency and activation status of circulating immune subpopulations on fresh whole blood. Multi-parametric marker sets (6-8 markers) will be used to analyse phenotype of immune subpopulations (TCD4+, TCD8+, Treg, T, NK, DC) and their activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86).

Analysis of the functional response of T cells, DC subsets and NK cells

* Analysis of tumor associated antigen (TAA) specific CD8 responses
* Quantification of circulating cytokines including mainly, but not limited to, IL-6, IL-2, IFN, VEGF, TNF, IL-15,F FGF using Luminex technology and VEGF, TGF, IL-7R by Elisa.

Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).

Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12

Ministry of Health, France

Cytheris, Inc.

Centre Leon Berard

Death

Carcinoma

Small Cell Lung Carcinoma

Triple Negative Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Thoracic Neoplasms

Respiratory Tract Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Gastrointestinal Agents

Pembrolizumab

Pancrelipase

Pancreatin

NT-I7 will be administered on Day 1 of alternate 21 day cycles (Cycle 1, 3, 5 etc.). Dosage will increase until the maximum tolerated dose (MTD) and/or the recommended phase 2 (RP2D) dose is reached.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) treated relapsed or refractory triple negative breast cancer (TNBC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) treated relapsed or refractory non-small cell lung cancer (NSCLC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) treated relapsed or refractory small cell lung cancer (SCLC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory microsatellite stable colorectal cancer (MSS-CRC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory pancreatic cancer (PC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory microsatellite stable colorectal cancer (MSS-CRC). Participants will receive 1200 µg/kg of NT-I7 and and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory pancreatic cancer (PC).Participants will receive 1200 µg/kg of NT-I7 and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory ovarian cancer (OC). Participants will receive a starting dose of 960 µg/kg of NT-I7 and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Administered by intramuscular (IM) injection

NT-I7

Administered by intravenous (IV) injection

pembrolizumab (KEYTRUDA®)

The main purposes of Phase 1b of this study are to determine the following in participants with advanced solid tumors:

* Safety and tolerability of NT-I7 in combination with pembrolizumab
* Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D)

The main purpose of Phase 2a of this study is to assess the preliminary anti-tumor activity of NT-I7 in combination with pembrolizumab in participants with checkpoint inhibitor (CPI) treated and naïve relapsed and refractory (R/R) tumors.

The main purpose of the Biomarker Cohort is to assess a potential correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits in participants with CPI-naïve R/R ovarian cancer (OC).

This is a multicenter, open-label Phase 1b/2a study of NT-I7 in combination with pembrolizumab. The study consists of a dose escalation phase (Phase 1b) followed by a dose expansion phase (Phase 2a) and a Biomarker Cohort.

The Phase 1b is designed to assess the safety and tolerability, including determination of the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7.

The main purpose of Phase 2a of this study is to assess the preliminary antitumor activity of NT-I7 in combination with pembrolizumab in participants with relapsed/refractory

* checkpoint inhibitor (CPI)-treated Triple Negative Breast Cancer (TNBC), Non-small Cell Lung Cancer (NSCLC), and Small Cell Lung Cancer (SCLC)
* checkpoint inhibitor (CPI)-naïve Microsatellite Stable Colorectal Cancer (MSS-CRC), and Pancreatic Cancer (PC) The Biomarker Cohort is designed to assess the correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits of NT-I7 in combination with pembrolizumab in participants with CPI naïve R/R Ovarian Cancer (OC).

NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

An Open-label Phase 1b/2a Study of NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Advanced Solid Tumors

* Incidence, nature and severity of Adverse Events (AEs) graded according to NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
* Incidence and nature of Dose-Limiting Toxicities (DLTs)

Statistical correlation of dose levels with safety and efficacy parameters.

TILs in tumor biopsy samples will be identified using a multi-spectral Immunofluorescence (IF) assay.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors	NCT05716295	Advanced or Met...	MDK-703 Checkpoint Inhi...	18 Years - 99 Years	Medikine, Inc.
A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors	NCT05716295	Advanced or Met...	MDK-703 Checkpoint Inhi...	18 Years - 99 Years	Medikine, Inc.
Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients	NCT01368107	Metastatic Brea...	placebo interleukin 7 interleukin 7 interleukin 7	18 Years -	Centre Leon Berard
NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors	NCT04332653	Any Advanced So... Triple Negative... Non Small Cell ... Small Cell Lung... Microsatellite ... Pancreatic Canc... Ovarian Cancer	NT-I7 pembrolizumab (...	18 Years -	NeoImmuneTech

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