Melanoma, Non-small Cell Lung Cancer
Conditions
Keywords
Invariant natural killer T cells (iNKT), Programmed Cell Death-1 (PD1, PD-1)
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.
Interventions
DRUGIMM60
IMM60, every 3 weeks for up to 6 cycles, intravenous (IV) infusion
DRUGPembrolizumab
Pembrolizumab, 200 mg, every 3 weeks for up to 35 cycles or approximately 2 years, intravenous (IV) infusion
Sponsors
Merck Sharp & Dohme LLC
iOx Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Primary Objective - Progression-free Survival | 12 months after last participant enrolled | 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 |
| Phase 1 Co-Primary Objective - Identify Maximum Tolerated Dose (MTD) | Assessed at the end of Cycle 1 for each patient (each Cycle is 28 days) | 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 | Through Phase 1 completion, an average of 1 year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of IMM60 - AUC (IMM60 arms only) | During Cycles 1 and 3 (each Cycle is 28 days) | IMM60 area under the curve (AUC) |
| Objective Response Rate (ORR) | 12 months after last participant enrolled | 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 characterize the safety of IMM60 alone or in combination with pembrolizumab | Through study completion, an average of 3 years | Frequency and severity of treatment-related adverse events (AEs) |
| To assess the ability of IMM60 to convert PD-L1 negative patients to PD-L1 positive | 12 months after last participant enrolled | Percent of PD-L1 negative (\<1%) NSCLC tumors that increase PD-L1 gene expression following treatment with IMM60 |
| To determine if IMM60 can sensitize patients with programmed death-ligand 1 (PD-L1) <1% NSCLC to PD-1 inhibition | 12 months after last participant enrolled | Objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in PDL1 \<1% NSCLC patients who receive IMM60 + pembrolizumab |
| To determine if IMM60 can restore sensitivity in PD-1 inhibitor-resistant melanoma (phase 2) | 12 months after last participant enrolled | 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) | During Cycles 1 and 3 (each Cycle is 28 days) | IMM60 maximal concentration (Cmax) |
Countries
Spain, United Kingdom, United States
Outcome results
None listed