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

NCT03252938 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: INSIGHT
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

NSCLC Adenocarcinoma; Urothelial Carcinoma; Solid Tumors; Peritoneal Carcinomatosis

Keywords

solid tumor; peritoneal carcinomatosis

Outcome Measures

Primary Outcomes (1)

• Feasibility rate

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

  10 weeks of treatment + 2 weeks of safety observation period

Secondary Outcomes (5)

• Incidence and severity of adverse events according to CTC criteria

  12 months of treatment + 12 months of Follow Up

• Response

  12 months of Follow Up

• Progression free survival

  12 months of Follow Up

• Overall survival

  12 months of Follow Up

• Immune response in whole blood and tumor tissue

  12 months of treatment + 12 months of Follow Up

Study Arms (5)

Solid tumors

EXPERIMENTAL

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)

Drug: IMP321

Solid tumors + peritoneal carcinomatosis

EXPERIMENTAL

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

Drug: IMP321

Solid tumors + chemotherapy

EXPERIMENTAL

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

Drug: IMP321

NSCLC + Avelumab/IMP321 therapy

EXPERIMENTAL

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 \[24 weeks\])

Drug: IMP321; Drug: Avelumab

Urothelial carcinoma + Avelumab/IMP321 combination therapy

EXPERIMENTAL

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 \[12 months\]

Drug: IMP321; Drug: Avelumab

Interventions

IMP321 DRUG

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

Also known as: LAG-3Ig fusion protein, efti, eftilagimod alfa

NSCLC + Avelumab/IMP321 therapy; Solid tumors; Solid tumors + chemotherapy; Solid tumors + peritoneal carcinomatosis; Urothelial carcinoma + Avelumab/IMP321 combination therapy

Avelumab DRUG

Avelumab i.v.

NSCLC + Avelumab/IMP321 therapy; Urothelial carcinoma + Avelumab/IMP321 combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed locally advanced (not manageable with curative intent) or metastatic solid tumor Specification for Stratum C: Only patients with NSCLC adenocarcinomas, (squamous or adenosquamous not permitted) who are scheduled to receive platin + pembrolizumab + pemetrexed standard treatment (only for Stratum C) Specification for Stratum E: Including only metastatic or irresectable locally advanced urothelial carcinomas - also refer to IC#14 below (only for Stratum E)
• Tumor is accessible for repeated injections and biopsies (only for Stratum A)
• Peritoneal carcinomatosis (only for Stratum B)
• Patient failed standard therapy or refused standard therapy or is intolerable towards standard therapy (Strata A, B, and D) or who receives Standard-of-Care first line treatment comprising platin + pembrolizumab + pemetrexed (only for Stratum C)
• Patient has not received more than 4 prior lines of therapy. Neoadjuvant/adjuvant treatment is not counted unless progression occurs \<6 months after completion of the treatment. In these cases, neoadjuvant/adjuvant treatment is counted as one prior line (only for Stratum D).
• Patients ≥ 18 years. Patients in reproductive age must be willing to use highly effective contraception during the study and 4 months after the end of the study (appropriate contraception is defined as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally.). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
• ECOG 0 or 1
• Adequate hematological, hepatic and renal function parameters:
• ANC (absolute neutrophil count) ≥ 1,500/µL
• Leukocytes ≥ 3,000/µL
• Platelets ≥ 75,000/µL (for Stratum D: ≥ 100,000/µL)
• Serum creatinine ≤ 1.5 x upper limit of normal, or GFR ≥ 50 mL/min (not applicable for patients not eligible for platinum-based therapy in Stratum E)
• Bilirubin ≤ 1.5 - 3 x upper limit of normal (for Stratum D: ≤ 1.5 x ULN)
• AST and ALT ≤ 3 x upper limit of normal (≤ 5 x if liver metastases are present) (for Stratum D: AST and ALT ≤ 2.5 x ULN; ≤ 5 x if liver metastases are present)
• Alkaline phosphatase ≤ 6 x upper limit of normal

You may not qualify if:

• Inability to understand the aims of the study and/or protocol procedures
• Bleeding ulcerative tumors or tumors requiring intratumoral injections of study drug into parenchymatous organs such as, but limited to liver, spleen or pancreas (only for Stratum A)
• Patients with contraindication versus a laparoscopy or refusing a laparoscopy (only for Stratum B)
• Hypersensitivity towards eftilagimod alpha, avelumab (only for Strata D and E) or any ingredient of the injection/infusion solutions
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Any concurrent other antineoplastic treatment including irradiation, or targeted small molecule therapy, or biological cancer therapy. (only Strata A, Band D)
• Prior PD-1/PD-L1 targeted therapy (only for Strata D).
• Cirrhosis of the liver (Child \> Grade A), pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
• Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV (for Stratum D: ≥ NYHA II) within 6 months prior to first dose of study treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of current NCI CTCAE version Grade \>2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, ventricular arrhythmias requiring medication or symptomatic pulmonary embolism
• Cerebral or leptomeningeal metastases Note: Subjects with previously treated brain metastases may participate if they meet the following criteria: 1) are stable for at least 28 days prior to the first dose of study treatment and if all neurologic symptoms returned to baseline; 2) have no evidence of new or enlarging brain metastases; and 3) have not been using steroids for at least 7 days prior to first dose of study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Chronic inflammatory bowel disease
• Active infection requiring systemic therapy at the start of study treatment or chronic infection or serious intercurrent infection within 4 weeks prior to first dose of study treatment
• QTcF \>480 ms, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP)
• Uncontrolled electrolyte disorders that can worsen the effects of a QTc-prolonging drug (e.g., hypocalcaemia, hypokalaemia, hypomagnesemia)
• Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Testing is not required in the absence of history.

Sponsors & Collaborators

• Immutep S.A.S.: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (12)

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Kliniken der Stadt Köln gGmbH, Studienzentrum der Lungenklinik, Krankenhaus Merheim

Cologne, 51109, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Agaplesion Markus Krankenhaus Frankfurter Diakonie Kliniken gGmbH

Frankfurt, 60431, Germany

Location

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Universität Gießen und Marburg GmbH

Giessen, 35392, Germany

Location

Hämatologisch Onkologische Praxis Eppendorf (HOPE)

Hamburg, 20249, Germany

Location

Marienhospital Herne, Klinik der Ruhr Universität Bochum, Klinik für Urologie

Herne, 44625, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm, Early Clinical Trials Unit (ECTU)

Ulm, 89081, Germany

Location

Helios Dr. Horst Schmidt Klinikum Wiesbaden

Wiesbaden, 65199, Germany

Location

MeSH Terms

Conditions

Peritoneal Neoplasms; Carcinoma, Transitional Cell

Interventions

soluble LAG-3 protein, human; avelumab

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Thorsten Götze, MD

  Institute of Clinical Cancer Research (IKF), UCT Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2017
• First Posted: August 17, 2017
• Study Start: August 15, 2017
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12)