IMM60 and Pembrolizumab in Melanoma and NSCLC

IMPORT-201: A Phase 1 First-in-Human Dose Finding/Randomized Phase 2 Study of IMM60 and Pembrolizumab for Advanced Melanoma and Metastatic NSCLC

The goal of this clinical trial is to learn about IMM60 with or without pembrolizumab in participants with advanced melanoma or non-small cell lung cancer. There are two phases:

• Phase 1: This phase is designed to learn about the safety of IMM60 with or without pembrolizumab and to find a safe dose to test in Phase 2.
• Phase 2: This phase is designed to learn whether IMM60 + pembrolizumab improves progression-free survival at 12 months compared to pembrolizumab alone in participants with non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: IMM60; Drug: Pembrolizumab

Detailed Description

This exploratory phase 1/phase 2 study is designed to establish a recommended phase 2 dose of IMM60 and provide preliminary estimates of safety and efficacy of IMM60 alone and in combination with pembrolizumab in participants with NSCLC and melanoma. In phase 1, initial safety will be assessed in a multiple dose escalation cohort for IMM60 alone, then for the IMM60 + pembrolizumab combination. Phase 2 of the study will recruit PD-1 pretreated melanoma participants and randomize PD-L1 > 50% total NSCLC participants 2:1 to IMM60 + pembrolizumab vs pembrolizumab alone. There is an additional cohort of PD-L1 < 1% NSCLC participants.

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

Contacts and Locations

• Study Contact: Name: Portage Clinical Trials; Email: clinicaltrials@portagebiotech.com

Study Locations

• Spain
  • Barcelona, Spain, 08041
    • Hospital de La Santa Creu i Sant Pau
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Málaga, Spain, 29011
    • Hospital Regional Universitario de Malaga
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen De La Macarena
  • Valencia, Spain, 46010
    • H. Clínico de Valencia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Català D'Oncologia-Hospital Universitari Germans Trias I Pujol
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Complexo Hospitalario Universitario A Coruña
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Hospital Xeral Álvaro Cunqueiro
• United Kingdom
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospital - Oncology
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute - Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital - Internal Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers, The State University of New Jersey - Robert Wood Johnson Medical School - The Cancer Institute of New Jersey (CINJ)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Next VA

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0 to 1
• Adequate organ function
• At least 1 lesion, not previously irradiated, that can be accurately measured on CT or MRI as defined by RECIST 1.1 criteria
• NSCLC cohorts: Histologically confirmed diagnosis of stage IV NSCLC
• NSCLC cohorts: Patients with adenocarcinoma histology must not have sensitizing epidermal growth factor receptor (EGFR) or ROS proto-oncogene 1 (ROS1) mutations or anaplastic lymphoma kinase (ALK) translocations
• NSCLC cohorts: Participants in NSCLC arms must have a PD-L1 assessment (PD-L1 immuno-histochemistry (IHC) 22C3 pharmDx)
• Melanoma cohorts: Unresectable stage III or IV, histologically confirmed diagnosis of cutaneous or unknown primary melanoma
• Melanoma cohorts: B-type Raf proto-oncogene (BRAF) mutation status available
• Male participants: Participant must agree to use contraception and refrain from sperm donation during the treatment period and for at least 120 days after the last dose of study intervention

• Female participants: Participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

  1. Not a woman of childbearing potential (WOCBP)
  2. A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 6 months after the last dose of study intervention

Exclusion Criteria:

• Has the following cardiac conditions:

  1. Corrected QT interval (QTc) > 450 ms
  2. Uncontrolled hypertension with blood pressure (BP) > 160/100 despite treatment
  3. Class II or greater heart failure as defined by the New York Heart Association
  4. Myocardial infarction within 6 months or angina requiring nitrate therapy more than once a week
• Another active malignancy within the past 2 years (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy are not excluded. Also, prostate, breast, and neuroendocrine tumors that are stable on hormonal treatment for a period of 1 year or more without the need to adjust dose are not excluded.)
• Has had an allogeneic tissue/solid organ transplant
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable.
• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Participants with an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids (in dosing exceeding 10 mg daily of prednisone equivalent) or immunosuppressive agents.
• Participants who are known to be serologically positive for Hepatitis B, Hepatitis C, or human immunodeficiency virus.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 IMM60 + pembrolizumab combination safety arm; Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the IMM60 dose escalation safety cohort.	Drug: IMM60; IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion; Other Names: PORT-2; Drug: Pembrolizumab; Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion; Other Names: KEYTRUDA®
Experimental: Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab); Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation safety cohorts.	Drug: IMM60; IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion; Other Names: PORT-2; Drug: Pembrolizumab; Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion; Other Names: KEYTRUDA®
Active Comparator: Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, pembrolizumab monotherapy); Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles.	Drug: Pembrolizumab; Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion; Other Names: KEYTRUDA®
Experimental: Phase 2 PD-L1 <1% NSCLC Cohort 2; Participants will be treated with one cycle of IMM60 with a tumor biopsy before and after, to determine any changes in PD-L1 expression. After this one cycle, the participants will receive the combination of IMM60 IV for up to 6 total cycles + pembrolizumab 200 mg every 3 weeks administered IV. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.	Drug: IMM60; IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion; Other Names: PORT-2; Drug: Pembrolizumab; Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion; Other Names: KEYTRUDA®
Experimental: Melanoma Cohort; IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.	Drug: IMM60; IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion; Other Names: PORT-2
Experimental: Phase 1 IMM60 dose escalation safety arm; 3 dose levels of IMM60 will be assessed (1, 3, 9 and 36 mg/m^2 administered IV every 3 weeks for up to 6 cycles)	Drug: IMM60; IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion; Other Names: PORT-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Co-Primary Objective - Identify Maximum Tolerated Dose (MTD)	To confirm the maximum tolerated dose (MTD) of IMM60 alone and in combination with pembrolizumab, defined as the highest dose level at which <2 out of 6 participants experience a dose-limiting toxicity	Assessed at the end of Cycle 1 for each patient (each Cycle is 28 days)
Phase 1 Co-Primary Objective - Safety	To characterize the safety of IMM60 alone and in combination with pembrolizumab, as assessed by the frequency of Grade 3 or higher treatment-related adverse events	Through Phase 1 completion, an average of 1 year
Phase 2 Primary Objective - Progression-free Survival	To compare the progression-free survival (PFS) rate at 12 months in the randomized arms comparing pembrolizumab alone versus IMM60 + pembrolizumab in patients with advanced PD-L1 ≥50% NSCLC	12 months after last participant enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the safety of IMM60 alone or in combination with pembrolizumab	Frequency and severity of treatment-related adverse events (AEs)	Through study completion, an average of 3 years
To determine if IMM60 can restore sensitivity in PD-1 inhibitor-resistant melanoma (phase 2)	Objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in melanoma patients who have progressed on PD-1, and have added IMM60	12 months after last participant enrolled
Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)	IMM60 maximal concentration (Cmax)	During Cycles 1 and 3 (each Cycle is 28 days)
Pharmacokinetics of IMM60 - AUC (IMM60 arms only)	IMM60 area under the curve (AUC)	During Cycles 1 and 3 (each Cycle is 28 days)
Objective Response Rate (ORR)	ORR is to be reported as the proportion of patients who have a Complete Response or Partial Response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1	12 months after last participant enrolled
To determine if IMM60 can sensitize patients with programmed death-ligand 1 (PD-L1) <1% NSCLC to PD-1 inhibition	Objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in PDL1 <1% NSCLC patients who receive IMM60 + pembrolizumab	12 months after last participant enrolled
To assess the ability of IMM60 to convert PD-L1 negative patients to PD-L1 positive	Percent of PD-L1 negative (<1%) NSCLC tumors that increase PD-L1 gene expression following treatment with IMM60	12 months after last participant enrolled

Collaborators and Investigators

• Sponsor: iOx Therapeutics
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Actual): April 22, 2024
• Study Completion (Actual): April 22, 2024

Study Registration Dates

• First Submitted: January 6, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Invariant natural killer T cells (iNKT)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: IMPORT-201; KEYNOTE-E69 (Other Identifier: Merck Sharp & Dohme LLC); 2022-003310-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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