Advanced Solid Tumors
Conditions
Keywords
Alkermes, IL-2, Interleukin-2, Oncology, Immuno-oncology, Cytokine, ALKS 4230, Pembrolizumab, Keytruda, PD-L1, Solid tumors, Immunotherapy, nemvaleukin alfa, ovarian, Head and Neck, NSCLC, Non small cell lung cancer, lung cancer, Gastric, Gastric Cancer, Gastroesophageal Cancer, Gastroesophageal junction (GEJ) adenocarcinoma, GEJ Cancer, adenocarcinoma
Brief summary
This study will characterize the safety and tolerability and identify the recommended Phase 2 dose (RP2D) of subcutaneous (SC) ALKS 4230 as monotherapy and in combination with pembrolizumab.
Detailed description
This study will evaluate ALKS 4230 administered SC as lead-in monotherapy and in combination with pembrolizumab in subjects with advanced solid tumors.
Interventions
BIOLOGICALALKS 4230
SC injection administered in the back of the arm or the abdomen
BIOLOGICALPembrolizumab
Administered as an intravenous (IV) infusion over 30 minutes
Sponsors
Mural Oncology, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Phase I the subject has histological or cytological evidence of a solid tumor. For Phase II the subject must have 1 of the specified adult solid tumor types: gastric, ovarian, lung, head and neck. * Subject must have at least one target lesion based on RECIST * Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 * Subjects must have adequate liver function * Subjects must have adequate kidney function * Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy or surgery * Subjects who have received radiation therapy must wait at least 4 weeks after their last radiation treatment before enrollment into the study * Females of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and on Day 1 before the first dose is administered * Subject will agree to follow contraceptive requirements defined in the protocol * Additional criteria may apply
Exclusion criteria
* Subject is currently pregnant, planning to become pregnant, or breastfeeding * Subjects with an active infection or with a fever ≥ 38.5°C within 3 days of the first scheduled day of dosing for Cycle 1 * Subjects with active or symptomatic central nervous system metastases are excluded. Subjects with central nervous system metastases are eligible for the study if the metastases have been treated by surgery and/or radiation therapy, the subject is off corticosteroids for at least 2 weeks, and the subject is neurologically stable * Subjects with known hypersensitivity to any components of ALKS 4230 or to pembrolizumab or any of its excipients * Subjects who require pharmacologic doses of systemic corticosteroids are excluded; replacement doses, topical, ophthalmologic, and inhalational steroids are permitted * Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and/or neuropathy * Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subjects to cooperate and participate in the study * The subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B or C, or active tuberculosis, or has a known history of tuberculosis * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs), and identify the RP2D of ALKS 4230 in Part A | From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months | Includes AEs that are both serious and drug-related |
| Number of subjects experiencing AEs that are both serious and drug-related in Part B | From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months | Includes AEs that are both serious and drug-related |
| Clinical Activity of combination treatment with ALKS 4230 and pembrolizumab in each Part B tumor type. | From time of therapy until the date of first documented tumor progression, assessed up to 24 months | Overall Response rate (ORR) will be based on investigator review of radiographic and photographic images |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response in subjects with PR/iPR | Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) | PR/iPR duration |
| Non-progression for Part B | Assessed up to 24 months | Time from first dose of SC ALKS 4230 to the time of progression or death |
| Overall survival for Part B | Assessed up to 24 months | Time from first dose of SC ALKS 4230 to the time of death |
| Proportion of subjects with objective evidence of Complete Response (CR)/immune CR (iCR) | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months | Overall response rate (ORR) will be based on investigator review of radiographic or photographic images |
| Serum will be assayed for the presence of anti-ALKS 4230 antibodies | From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months | Results will be summarized by dose level |
| Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points | From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months | Results will be summarized by dose level |
| Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points | From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months | Results will be summarized by dose level |
| Serum concentrations of ALKS 4230 will be determined at various time points | From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months | Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level |
| Proportion of subjects with objective evidence of Partial Response (PR)/immune PR (iPR) | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months | ORR will be based on investigator review of radiographic or photographic images |
| Duration of response in subjects with CR/iCR | Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) | CR/iCR duration |
Countries
Canada, Netherlands, South Korea, Spain, Taiwan, United States
Outcome results
None listed