Intratumoral Injection of IP-001 Following Thermal Ablation in Patients With CRC, NSCLC, and STS (INJECTABL-1)

Intratumoral Injection of IP-001 Following Thermal Ablation in Patients With Advanced Solid Tumors. A Multicenter Phase 1b/2a Trial in Colorectal Cancer, Non-small Cell Lung Cancer, and Soft Tissue Sarcoma Patients

The goal of this clinical trial is to determine the safety and efficacy of IP-001 for intratumoral injection administration following thermal ablation of a solid tumor.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma; Nonsmall Cell Lung Cancer; Metastatic Solid Tumor; Colon Cancer
• Intervention / Treatment: Drug: 1.0% IP-001 for Injection

Detailed Description

The therapeutic approach taken by this clinical trial may offer patients a therapeutic benefit after failure of standard chemotherapy and immunotherapy.

Patients giving written informed consent will undergo screening during the Pretreatment Period to determine eligibility for trial entry. The Pretreatment Period will include collection and recording of medical history, concomitant medications, baseline symptoms, previous therapies, and baseline assessments. The patient's baseline tumor burden will be recorded with radiological assessments, along with analyzing location and size of tumors to identify and characterize target tumor(s) that will be treated and/or followed during the clinical trial.

If confirmed eligible for the study, the patient will advance into the Treatment Period. During the Treatment Period, patients will receive a routine radiofrequency ablation (RFA), followed by an injection of investigational product (IP-001 for Injection) into the tumor. Patients can be treated every 6 weeks for up to 4 treatments with RFA + IP-001 for Injection.

A patient will move to the 6-month Follow-up Period when the patient has completed 4 treatment cycles or if the decision is made that no subsequent treatments will be administered. During the Follow-up Period, there will be a Follow-up Visit every 6 weeks for 5 visits, at disease progression, or prior to the start of a new antineoplastic treatment.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sara Mcloud Tyley; Phone Number: +44 7342 061 439; Email: sara.mcloudtyley@iqvia.com
• Study Contact Backup: Name: Jane Bierman; Phone Number: +31 64 523 4949; Email: jane.bierman2@iqvia.com

Study Locations

• France
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonie
    • Contact: Antoine Italiano, MD; Phone Number: +33 5 56 33 32 44; Email: a.italiano@bordeaux.unicancer.fr
  • Paris, France, 75013
    • Recruiting
    • Hospitalier Pitie-Salpetriere
    • Contact: Jean-Philippe Spano, MD; Phone Number: +33 1 42 16 04 72; Email: jean-philippe.spano@aphp.fr
  • Suresnes, France, 92150
    • Recruiting
    • Hôpital Foch
    • Contact: Jaafar Bennouna, MD; Phone Number: +33 1 46 25 19 75; Email: j.bennouna@hopital-foch.com
  • Villejuif, France, 94805
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Thierry de Baere, MD; Phone Number: +33 1 42 11 54 28; Email: thierry.debaere@gustaveroussy.fr
• Germany
  • Frankfurt, Germany, 60590
    • Recruiting
    • Johann Wolfgang Goethe-Univresitat Frankfurt/Main
    • Contact: Thomas Vogl; Email: t.vogl@em.uni-frankfurt.de
  • Heilbronn, Germany, 74078
    • Recruiting
    • SLK-Kliniken Heilbronn GmbH
    • Contact: Uwe Martens; Phone Number: +49-7131-49-28001; Email: uwe.martens@skl-kliniken.de
  • Munich, Germany, 81925
    • Recruiting
    • München Klinik Bogenhausen
    • Contact: Thomas Helmberger; Phone Number: 00498992702201; Email: thomas.helmberger@muenchen-klinik.de
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Recruiting
    • IOSI Ospedale San Giovanni Bellinzona
    • Contact: Sara DeDosso, MD; Phone Number: +41 91 811 86 67; Email: sara.dedosso@eoc.ch
    • Contact: Ilaria Colombo, MD; Phone Number: +41 91 811 81 94; Email: ilaria.colombo@eoc.ch
  • Bern, Switzerland, CH-3010
    • Recruiting
    • Inselspital Universitatsspital, Bern
    • Contact: Attila Kollar, MD; Phone Number: +41 31 632 41 14; Email: attila.kollar@insel.ch
    • Contact: Sabine Schmid, MD; Phone Number: 0041 31 632 41 14; Email: sabine.schmid@insel.ch
  • Chur, Switzerland, 7000
    • Recruiting
    • Kantonsspital Graubunden
    • Contact: Sara Bastian, MD; Phone Number: +41 81 256 68 84; Email: sara.bastian@ksgr.ch
    • Contact: Michael Mark, MD; Phone Number: +41 81 256 74 25; Email: Michael.Mark@ksgr.ch
  • St. Gallen, Switzerland, CH-9007
    • Recruiting
    • Kantonsspital St. Gallen
    • Contact: Markus Jörger, MD; Phone Number: +41 76 559 10 70; Email: markus.joerger@kssg.ch
    • Contact: Dagmar Hess, MD; Phone Number: +41 71 494 10 80; Email: dagmar.hess@kssg.ch
• United Kingdom
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals
    • Contact: Steve Bandula, MD; Email: s.bandula@ucl.ac.uk
  • Oxford, United Kingdom, OX3 7LJ
    • Recruiting
    • Churchill Hospital
    • Contact: Mark Middleton, MD
• United States
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Recruiting
      • Miami Cardiac & Vascular Institute
      • Contact: Govindarajan Narayanan, MD; Email: govindarajann@baptisthealth.net
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Physicians, PSC
      • Contact: Robert Martin, PhD, MD; Phone Number: 502-562-4158; Email: robert.martin@louisville.edu
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Stephenson Cancer Center
      • Contact: Abdul R Naqash, MD; Email: abdulrafeh-naqash@ouhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Stage 3 or Stage 4 CRC, NSCLC, or STS who have failed, are ineligible, refused, or become intolerant to at least first line (but no more than 4 lines) of systemic therapy
2. Life expectancy of > 6 months. Only have lesions with the longest diameter of ≤ 5 cm.
3. Presence of at least one non-bone tumor lesion that is ablation-accessible, with a minimum size of 1.0 cm.
4. Measurable disease according to RECIST 1.1.
5. Age ≥ 18 years.
6. ECOG performance status 0-1.
7. Bone marrow function: neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, hemoglobin ≥ 90 g/L.
8. Adequate hematological function defined by white blood cell count ≥ 2.5 × 109/L with absolute neutrophil count ≥ 1.5 × 109/L, and hemoglobin ≥ 9 g/dL (transfusions allowed on study).
9. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and aspartate transaminase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all patients, or for patients with documented metastatic disease to the liver and AST and ALT levels ≤ 5 × ULN. Patients with documented Gilbert disease are allowed if total bilirubin is less than 3 × ULN.
10. Adequate renal function defined by an estimated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
11. Men and women with childbearing potential agree to use effective contraception. Women of childbearing potential must have a negative pregnancy test (serum) before inclusion.

Exclusion Criteria:

1. Known allergic reaction to shellfish, crabs, crustaceans, or any trial components, used in trial treatment.
2. Malignant primary brain tumors or evidence of brain metastases or leptomeningeal disease.
3. Patients who have received chemotherapy, radiotherapy, immunotherapy, or concurrent or recent treatment with any other investigational agents within 21 days prior to treatment.
4. Patients who have not recovered to common terminology criteria for adverse events (CTCAE) Grade ≤ 1 from all side effects of prior therapies except for residual toxicities.
5. Patients with a history of malignancy, with the exception of non-melanoma skin cancers and in situ cancers.
6. Concomitant treatment with systemic corticosteroids (10 mg prednisolone or equivalent) or other immunosuppressive therapy.
7. Anti-coagulation therapies which cannot be stopped 24 hours prior to trial treatment.
8. Severe or uncontrolled cardiovascular disease (congestive heart failure New York Heart Association classification III or IV).
9. Documented HIV positive.
10. Active Hepatitis C or Hepatitis B Viral infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colorectal Cancer (CRC); Radiofrequency ablation (RFA) followed by an intratumoral injection of IP-001.	Drug: 1.0% IP-001 for Injection; 4 mL 1.0% IP-001 for Injection following RFA every 6 weeks for up to 4 treatments.; Other Names: IP-001
Experimental: Non-Small Cell Lung Cancer (NSCLC); Radiofrequency ablation (RFA) followed by an intratumoral injection of IP-001.	Drug: 1.0% IP-001 for Injection; 4 mL 1.0% IP-001 for Injection following RFA every 6 weeks for up to 4 treatments.; Other Names: IP-001
Experimental: Soft Tissue Sarcoma (STS); Radiofrequency ablation (RFA) followed by an intratumoral injection of IP-001.	Drug: 1.0% IP-001 for Injection; 4 mL 1.0% IP-001 for Injection following RFA every 6 weeks for up to 4 treatments.; Other Names: IP-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	The assessment of safety will be based on incidence of adverse events.	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Disease control according to Immune Response Evaluation Criteria in Solid Tumors for immune-based treatment (iRECIST) (iDC)	An iDC is defined as any complete response (CR or iCR), partial response (PR or iPR), or stable disease (SD or iSD) for 12 weeks according to iRECIST achieved during the trial until disease progression according to iRECIST, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: Disease control according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (DC)	A DC is defined as any complete response (CR), partial response (PR) or stable disease (SD) for 12 weeks from start of treatment according to RECIST 1.1 achieved during trial until disease progression according to iRECEST, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: Objective response according to iRECIST (iOR)	An iOR is defined as any complete response (CR or iCR) or partial response (PR or iPR) according to iRECIST achieved during the trial until disease progression according to iRECIST, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: Duration of response according to iRECIST (iDOR)	An iDOR is defined as the time from the first documentation of iOR until disease progression according to iRECIST (iPD) or death from any cause. iPD is defined as the time point of first iUPD without subsequent iSD, iPR or iCR before trial discontinuation.	Up to 12 weeks
Efficacy: Progression-free survival according to iRECIST (iPFS)	An iPFS is defined as the time from treatment start until disease progression according to iRECIST (iPD) or death from any cause, whichever occurs first.	Up to 12 weeks
Efficacy: Objective response according to RECIST 1.1 (OR)	An OR is defined as any complete response (CR) or partial response (PR) according to RECIST 1.1 achieved during trial until disease progression, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: Duration of response according to RECIST 1.1 (DOR)	A DOR is defined as the time from the first documentation of OR until disease progression according to RECIST 1.1, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: Progression-free survival according to RECIST 1.1 (PFS)	A PFS is defined as the time from treatment start until disease progression according to RECIST 1.1, or death from any cause, whichever occurs first.	Up to 12 weeks
Efficacy: Time to response according to iRECIST 1.1 (iTTR)	An iTTR is defined as the time from start of trial treatment until iOR according to iRECIST achieved during the trial.	Up to 12 weeks
Efficacy: Time to response according to RECIST 1.1 (TTR)	A TTR is defined as the time from treatment start until OR according to iRECIST achieved during the trial.	Up to 12 weeks
Efficacy: Disease-free survival (DFS)	A DFS is defined as the time from start of treatment that the patient survives without any signs or symptoms of cancer or death from any cause, whichever occurs first.	Up to 12 weeks
Efficacy: Overall survival (OS)	An OS is defined as the time from start of treatment until death from any cause.	Up to 12 weeks
Efficacy: OR of the injected lesions according to RECIST 1.1	An OR of the ablated and injected (treated) lesions will be assessed using RECIST 1.1.	Up to 12 weeks
Efficacy: OR of the non-injected lesions according to RECIST 1.1	An OR of the non-ablated and non-injected (untreated) lesions will be assessed using the RECIST 1.1 until disease progression according to RECIST 1.1, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: iOR of the injected lesions according to iRECIST	An iOR of the ablated and injected (treated) lesions will be assessed using the iRECIST until disease progression according to RECIST 1.1, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks
Efficacy: iOR of the non-injected lesions according to iRECIST	An iOR of the non-ablated and non-injected (untreated) lesions will be assessed using the iRECIST until disease progression according to RECIST 1.1, death from any cause, or start of a subsequent anticancer treatment, whichever occurs first.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Immunophotonics, Inc.
• Investigators: Principal Investigator: Markus Jorger, MD, Cantonal Hospital of St. Gallen; Study Director: Diane Beatty, PhD, Immunophotonics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: December 22, 2022
• First Submitted That Met QC Criteria: January 8, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Melanoma; Thermal ablation; Soft tissue sarcoma; Intratumoral injection; Advanced solid tumors; Abscopal effect; Tumor ablation; Interventional oncology; IP-001; Anti-cancer drug or therapy; Phase lb/lla; Systemic immune response; Interventional immuno-oncology; T-cell stimulation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Sarcoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: IP-IIO-622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No