Clinical trial NCT05709821: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Melanoma
Keywords: Invariant natural killer T cells (iNKT)
Programmed Cell Death-1 (PD1, PD-1)
Lead sponsor: Portage Biotech
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2023-02-02
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Phase 1 Co-Primary Objective - Identify Maximum Tolerated Dose (MTD)
timeFrame: Assessed at the end of Cycle 1 for each patient (each Cycle is 28 days)
measure: Phase 1 Co-Primary Objective - Safety
timeFrame: Through Phase 1 completion, an average of 1 year
measure: Phase 2 Primary Objective - Progression-free Survival
timeFrame: 12 months after last participant enrolled
Secondary outcomes:
measure: To characterize the safety of IMM60 alone or in combination with pembrolizumab
timeFrame: Through study completion, an average of 3 years
measure: To determine if IMM60 can restore sensitivity in PD-1 inhibitor-resistant melanoma (phase 2)
timeFrame: 12 months after last participant enrolled
measure: Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)
timeFrame: During Cycles 1 and 3 (each Cycle is 28 days)
measure: Pharmacokinetics of IMM60 - AUC (IMM60 arms only)
timeFrame: During Cycles 1 and 3 (each Cycle is 28 days)
measure: Objective Response Rate (ORR)
timeFrame: 12 months after last participant enrolled
measure: To determine if IMM60 can sensitize patients with programmed death-ligand 1 (PD-L1) <1% NSCLC to PD-1 inhibition
timeFrame: 12 months after last participant enrolled
measure: To assess the ability of IMM60 to convert PD-L1 negative patients to PD-L1 positive
timeFrame: 12 months after last participant enrolled
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute - Medicine
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital - Internal Medicine
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers, The State University of New Jersey - Robert Wood Johnson Medical School - The Cancer Institute of New Jersey (CINJ)
state: New Jersey
city: Fairfax
country: United States
facility: Next VA
state: Virginia
city: Badalona
country: Spain
facility: Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
state: Galicia
city: Vigo
country: Spain
facility: Hospital Xeral Álvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De La Macarena
city: Valencia
country: Spain
facility: H. Clínico de Valencia
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital - Oncology
Study officials:
References: