IMM60 and Pembrolizumab in Melanoma and NSCLC

NCT05709821 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: IMPORT-201KEYNOTE-E692022-003310-36
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 14

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.

Conditions

Non-small Cell Lung Cancer; Melanoma

Keywords

Invariant natural killer T cells (iNKT); Programmed Cell Death-1 (PD1, PD-1)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• To characterize the safety of IMM60 alone or in combination with pembrolizumab

  Through study completion, an average of 3 years

• To determine if IMM60 can restore sensitivity in PD-1 inhibitor-resistant melanoma (phase 2)

  12 months after last participant enrolled

• Pharmacokinetics of IMM60 - Cmax (IMM60 arms only)

  During Cycles 1 and 3 (each Cycle is 28 days)

• Pharmacokinetics of IMM60 - AUC (IMM60 arms only)

  During Cycles 1 and 3 (each Cycle is 28 days)

• Objective Response Rate (ORR)

  12 months after last participant enrolled

Study Arms (6)

Phase 1 IMM60 dose escalation safety arm

EXPERIMENTAL

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

Phase 1 IMM60 + pembrolizumab combination safety arm

EXPERIMENTAL

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; Drug: Pembrolizumab

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

EXPERIMENTAL

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; Drug: Pembrolizumab

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

ACTIVE COMPARATOR

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

Drug: Pembrolizumab

Phase 2 PD-L1 <1% NSCLC Cohort 2

EXPERIMENTAL

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; Drug: Pembrolizumab

Melanoma Cohort

EXPERIMENTAL

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

Interventions

IMM60 DRUG

IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion

Also known as: PORT-2

Melanoma Cohort; Phase 1 IMM60 + pembrolizumab combination safety arm; Phase 1 IMM60 dose escalation safety arm; Phase 2 PD-L1 <1% NSCLC Cohort 2; Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab)

Pembrolizumab DRUG

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

Also known as: KEYTRUDA®

Phase 1 IMM60 + pembrolizumab combination safety arm; Phase 2 PD-L1 <1% NSCLC Cohort 2; Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab); Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, pembrolizumab monotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• iOx Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (14)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Dana-Farber Cancer Institute - Medicine

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital - Internal Medicine

Detroit, Michigan, 48202, United States

Location

Rutgers, The State University of New Jersey - Robert Wood Johnson Medical School - The Cancer Institute of New Jersey (CINJ)

New Brunswick, New Jersey, 08901, United States

Location

Next VA

Fairfax, Virginia, 22031, United States

Location

Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, Galicia, 15006, Spain

Location

Hospital Xeral Álvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29011, Spain

Location

Hospital Universitario Virgen De La Macarena

Seville, 41009, Spain

Location

H. Clínico de Valencia

Valencia, 46010, Spain

Location

Nottingham University Hospital - Oncology

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: February 2, 2023
• Study Start: November 15, 2023
• Primary Completion: April 22, 2024
• Study Completion: April 22, 2024
• Last Updated: April 24, 2024

Record last verified: 2024-04

Locations

GB (1); US (5); ES (8)