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IMM60 and Pembrolizumab in Melanoma and NSCLC

Primary Purpose

Non-small Cell Lung Cancer, Melanoma

Status
Not yet recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
IMM60
Pembrolizumab
Sponsored by
iOx Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Invariant natural killer T cells (iNKT), Programmed Cell Death-1 (PD1, PD-1)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: Not a woman of childbearing potential (WOCBP) 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: Corrected QT interval (QTc) > 450 ms Uncontrolled hypertension with blood pressure (BP) > 160/100 despite treatment Class II or greater heart failure as defined by the New York Heart Association 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.

Sites / Locations

  • Dana-Farber Cancer Institute - Medicine
  • Henry Ford Hospital - Internal Medicine
  • Rutgers, The State University of New Jersey - Robert Wood Johnson Medical School - The Cancer Institute of New Jersey (CINJ)
  • Next VA
  • Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
  • Complexo Hospitalario Universitario A Coruña
  • Hospital Xeral Álvaro Cunqueiro
  • Hospital de La Santa Creu i Sant Pau
  • Hospital Universitario 12 de Octubre
  • Hospital Regional Universitario de Málaga
  • Hospital Universitario Virgen De La Macarena
  • H. Clínico de Valencia
  • Nottingham University Hospital - Oncology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Experimental

Experimental

Arm Label

Phase 1 IMM60 dose escalation safety arm

Phase 1 IMM60 + pembrolizumab combination safety arm

Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab)

Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, pembrolizumab monotherapy)

Phase 2 PD-L1 <1% NSCLC Cohort 2

Melanoma Cohort

Arm Description

3 dose levels of IMM60 will be assessed (1, 3, and 9 mg/m^2 administered IV every 3 weeks for up to 6 cycles)

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.

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.

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles.

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.

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.

Outcomes

Primary Outcome Measures

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
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
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

Secondary Outcome Measures

To characterize the safety of IMM60 alone or in combination with pembrolizumab
Frequency and severity of treatment-related adverse events (AEs)
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
Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)
IMM60 maximal concentration (Cmax)
Pharmacokinetics of IMM60 - AUC (IMM60 arms only)
IMM60 area under the curve (AUC)
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
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
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

Full Information

First Posted
January 6, 2023
Last Updated
July 3, 2023
Sponsor
iOx Therapeutics
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05709821
Brief Title
IMM60 and Pembrolizumab in Melanoma and NSCLC
Official Title
IMPORT-201: A Phase 1 First-in-Human Dose Finding/Randomized Phase 2 Study of IMM60 and Pembrolizumab for Advanced Melanoma and Metastatic NSCLC
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 18, 2023 (Anticipated)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
iOx Therapeutics
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, Melanoma
Keywords
Invariant natural killer T cells (iNKT), Programmed Cell Death-1 (PD1, PD-1)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 IMM60 dose escalation safety arm
Arm Type
Experimental
Arm Description
3 dose levels of IMM60 will be assessed (1, 3, and 9 mg/m^2 administered IV every 3 weeks for up to 6 cycles)
Arm Title
Phase 1 IMM60 + pembrolizumab combination safety arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, pembrolizumab monotherapy)
Arm Type
Active Comparator
Arm Description
Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles.
Arm Title
Phase 2 PD-L1 <1% NSCLC Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Melanoma Cohort
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IMM60
Other Intervention Name(s)
PORT-2
Intervention Description
IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Phase 1 Co-Primary Objective - Identify Maximum Tolerated Dose (MTD)
Description
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
Time Frame
Assessed at the end of Cycle 1 for each patient (each Cycle is 28 days)
Title
Phase 1 Co-Primary Objective - Safety
Description
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
Time Frame
Through Phase 1 completion, an average of 1 year
Title
Phase 2 Primary Objective - Progression-free Survival
Description
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
Time Frame
12 months after last participant enrolled
Secondary Outcome Measure Information:
Title
To characterize the safety of IMM60 alone or in combination with pembrolizumab
Description
Frequency and severity of treatment-related adverse events (AEs)
Time Frame
Through study completion, an average of 3 years
Title
To determine if IMM60 can restore sensitivity in PD-1 inhibitor-resistant melanoma (phase 2)
Description
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
Time Frame
12 months after last participant enrolled
Title
Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)
Description
IMM60 maximal concentration (Cmax)
Time Frame
During Cycles 1 and 3 (each Cycle is 28 days)
Title
Pharmacokinetics of IMM60 - AUC (IMM60 arms only)
Description
IMM60 area under the curve (AUC)
Time Frame
During Cycles 1 and 3 (each Cycle is 28 days)
Title
Objective Response Rate (ORR)
Description
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
Time Frame
12 months after last participant enrolled
Title
To determine if IMM60 can sensitize patients with programmed death-ligand 1 (PD-L1) <1% NSCLC to PD-1 inhibition
Description
Objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in PDL1 <1% NSCLC patients who receive IMM60 + pembrolizumab
Time Frame
12 months after last participant enrolled
Title
To assess the ability of IMM60 to convert PD-L1 negative patients to PD-L1 positive
Description
Percent of PD-L1 negative (<1%) NSCLC tumors that increase PD-L1 gene expression following treatment with IMM60
Time Frame
12 months after last participant enrolled

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Not a woman of childbearing potential (WOCBP) 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: Corrected QT interval (QTc) > 450 ms Uncontrolled hypertension with blood pressure (BP) > 160/100 despite treatment Class II or greater heart failure as defined by the New York Heart Association 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Portage Clinical Trials
Email
clinicaltrials@portagebiotech.com
Facility Information:
Facility Name
Dana-Farber Cancer Institute - Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Henry Ford Hospital - Internal Medicine
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Rutgers, The State University of New Jersey - Robert Wood Johnson Medical School - The Cancer Institute of New Jersey (CINJ)
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Next VA
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Complexo Hospitalario Universitario A Coruña
City
A Coruña
State/Province
Galicia
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Xeral Álvaro Cunqueiro
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36312
Country
Spain
Facility Name
Hospital de La Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Regional Universitario de Málaga
City
Málaga
ZIP/Postal Code
29011
Country
Spain
Facility Name
Hospital Universitario Virgen De La Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
H. Clínico de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Nottingham University Hospital - Oncology
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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IMM60 and Pembrolizumab in Melanoma and NSCLC

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