IMM60 and Pembrolizumab in Melanoma and NSCLC

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05709821
• Other study ID #: IMPORT-201
• Secondary ID: KEYNOTE-E692022-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 15, 2023
• Est. completion date: April 22, 2024

Study information

• Verified date: April 2024
• Source: Portage Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 22, 2024
• Est. primary completion date: April 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Non-small Cell Lung Cancer

Intervention

Drug:
• IMM60
IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion
• Pembrolizumab
Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña	Galicia
Spain	Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Hospital Universitario Virgen De La Macarena	Sevilla
Spain	H. Clínico de Valencia	Valencia
Spain	Hospital Xeral Álvaro Cunqueiro	Vigo	Pontevedra
United Kingdom	Nottingham University Hospital - Oncology	Nottingham
United States	Dana-Farber Cancer Institute - Medicine	Boston	Massachusetts
United States	Henry Ford Hospital - Internal Medicine	Detroit	Michigan
United States	Next VA	Fairfax	Virginia
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Rutgers, The State University of New Jersey - Robert Wood Johnson Medical School - The Cancer Institute of New Jersey (CINJ)	New Brunswick	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
iOx Therapeutics	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	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
Secondary	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
Secondary	Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)	IMM60 maximal concentration (Cmax)	During Cycles 1 and 3 (each Cycle is 28 days)
Secondary	Pharmacokinetics of IMM60 - AUC (IMM60 arms only)	IMM60 area under the curve (AUC)	During Cycles 1 and 3 (each Cycle is 28 days)
Secondary	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
Secondary	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
Secondary	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