Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Feasibility and Safety of IMP321 for Advanced Stage Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03252938
Recruitment Status : Recruiting
First Posted : August 17, 2017
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest

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

Condition or disease Intervention/treatment Phase
Solid Tumors Peritoneal Carcinomatosis Drug: IMP321 Drug: Avelumab Phase 1

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Explorative, Single Center, Open-labeled, Phase I Study to Evaluate the Feasibility and Safety of Intra-tumoral, Intra-peritoneal, and Subcutaneous Injections With IMP321 (LAG-3Ig Fusion Protein) for Advanced Stage Solid Tumor Entities
Actual Study Start Date : August 15, 2017
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Solid tumors
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
LAG-3Ig fusion protein, highly potent activator of antigen presenting cells
Other Name: LAG-3Ig fusion protein

Experimental: Solid tumors + peritoneal carcinomatosis
Biweekly intra-peritoneal, escalating doses of IMP321 (1 mg, 3 mg, 6 mg, 12 mg and 30 mg)
Drug: IMP321
LAG-3Ig fusion protein, highly potent activator of antigen presenting cells
Other Name: LAG-3Ig fusion protein

Experimental: Solid tumors + chemotherapy
Subcutaneous (s.c.) injections with the optimal dose of IMP321 defined in the AIPAC trial for a maximum of 24 weeks
Drug: IMP321
LAG-3Ig fusion protein, highly potent activator of antigen presenting cells
Other Name: LAG-3Ig fusion protein

Experimental: Solid tumors + Avelumab/IMP321 therapy

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

Drug: Avelumab
Avelumab i.v.




Primary Outcome Measures :
  1. Feasibility rate [ Time Frame: 10 weeks of treatment + 2 weeks of safety observation period ]
    Rate of patients receiving the protocol treatment without occurrence of a dose limiting toxicity


Secondary Outcome Measures :
  1. Incidence and severity of adverse events according to CTC criteria [ Time Frame: 12 months of treatment + 12 months of Follow Up ]
    Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

  2. Response [ Time Frame: 12 months of Follow Up ]
    Objective response rate according to RECIST 1.1 and endoscopic response criteria

  3. Progression free survival [ Time Frame: 12 months of Follow Up ]
    PFS will be measured as time from inclusion until disease progression or death of any cause

  4. Overall survival [ Time Frame: 12 months of Follow Up ]
    OS will be measured as time from inclusion to death of any cause

  5. Immune response in whole blood and tumor tissue [ Time Frame: 12 months of treatment + 12 months of Follow Up ]
    Peripheral blood monocyte number and CD8 T-cell number, associated activation markers, tumor-infiltrating immune cells



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed locally advanced or metastatic solid tumor
  2. Tumor is accessible for repeated injections and biopsies (only for Stratum A)
  3. Peritoneal carcinomatosis (only for Stratum B)
  4. Patient failed standard therapy or refused standard therapy or is intolerable towards standard therapy (Strata A, B, D) or who receives standard-of-care therapy indicated for his/her tumor entity (only for Stratum C)
  5. 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)
  6. Patient does not receive a concurrent chemotherapy (only for Strata A, B, D)
  7. Female and male 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. Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
  8. ECOG 0 or 1
  9. Adequate hematological, hepatic and renal function parameters:

    • ANC (absolute neutrophil count) ≥ 1.500/µl (for Stratum D: >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
    • 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
    • Hemoglobin ≥ 9g/dL
  10. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile.
  11. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures
  12. Evidence of measurable disease as defined by RECIST v1.1 (only for Stratum D)
  13. Expected survival > 3 months
  14. Resolution of toxicity associated with prior or current therapy to grade <2 (except for alopecia and transaminases in case of liver metastases)

Exclusion Criteria:

  1. Inability to understand the aims of the study and/or protocol procedures
  2. 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)
  3. Patients with contraindication versus a laparoscopy or refusing a laparoscopy (only for Stratum B)
  4. Hypersensitivity to IMP321, avelumab (only for Stratum D) or any ingredient of the injection solution
  5. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  6. Currently receiving any other antineoplastic treatment including irradiation, or targeted small molecule therapy, or biological cancer therapy, or less than 4 weeks since completion of these therapies and first dose of study treatment (only Strata A, B and D)
  7. Prior PD-1/PDL-1 targeted therapy (only for Stratum D)
  8. Cirrhosis of the liver (Child > Grade A), pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
  9. 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
  10. 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.
  11. Chronic inflammatory bowel disease
  12. 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
  13. 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)
  14. Uncontrolled electrolyte disorders that can worsen the effects of a QTc-prolonging drug (e.g., hypocalcaemia, hypokalaemia, hypomagnesemia)
  15. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
  16. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Note: Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).
  17. History or evidence of interstitial lung disease, active non-infectious pneumonitis or active tuberculosis
  18. Active or prior autoimmune disease requiring immunosuppressive therapy that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  19. Known history of immune-mediated colitis, pneumonitis, pulmonary fibrosis (only for Stratum D)
  20. Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study.
  21. Any condition requiring continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment

21. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is shorter, prior to start of study treatment. Intranasal, inhaled or topical steroids, eye drops or local steroid injection (eg, intra-articular injection), steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication) and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.

22. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is shorter, prior to start of study treatment 23. Any previous venous thromboembolism > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within the last 6 months 24. Past history of severe allergic episodes and/ or Quincke's oedema 25. Prior organ transplantation or stem cell transplantation 26. On-treatment participation in another clinical study in the period 30 days prior to start of study treatment and during the study 27. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4) 28. Pregnancy or lactation 29. Planned intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal gland, pancreas) 30. Life-threatening illness unrelated to cancer 31. History of irAEs of CTCAE Grade 4 requiring steroid treatment (only for Stratum D) 32. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade > 1); however, alopecia, sensory neuropathy Grade <=2, or other Grade <=2 AEs not constituting a safety risk based on investigator's judgment are acceptable (only for Stratum D) 33. Other severe acute or chronic medical conditions, psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03252938


Contacts
Layout table for location contacts
Contact: Salah-Eddin Al-Batran, MD +49 69 7601 ext 4420 albatran@ikf-khnw.de
Contact: Regina Eickhoff, PhD +49 69 7601 ext 4165 eickhoff.regina@ikf-khnw.de

Locations
Layout table for location information
Germany
Krankenhaus Nordwest Recruiting
Frankfurt, Germany, 60488
Contact: Salah-Eddin Al-Batran, MD    +4969 7601 ext 4420    albatran.salah@khnw.de   
Contact: Eickhoff Regina, PhD    +4969 7601 ext 4165    eickhoff.regina@ikf-khnw.de   
Principal Investigator: Salah-Eddin Al-Batran, MD         
Sponsors and Collaborators
IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest
Investigators
Layout table for investigator information
Principal Investigator: Salah-Eddin Al-Batran, MD Institute of Clinical Cancer Research (IKF), UCT Frankfurt, Germany

Layout table for additonal information
Responsible Party: IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest
ClinicalTrials.gov Identifier: NCT03252938     History of Changes
Other Study ID Numbers: INSIGHT
First Posted: August 17, 2017    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No IPD will be shared.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest:
solid tumor
peritoneal carcinomatosis

Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Peritoneal Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs