Brain Tumor, Glioma Glioblastoma Multiforme, Glioma, Malignant, Lung Cancer, Non-Small Cell Adenocarcinoma, Non Small Cell Lung Cancer, Solid Tumor
Conditions
Keywords
MTAP, PRMT5 inhibitor, CDK 4/6, abemaciclib, Tango
Brief summary
This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an MTAP loss. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific solid tumor types with a confirmed MTAP loss. The study drug, TNG456, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 191 participants.
Detailed description
This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed MTAP loss in their tumor. The Phase 1 portion is a dose escalation study of oral TNG456 administered as a single agent and in combination with oral abemaciclib in solid tumor patients with confirmed MTAP loss. In the Phase 2 expansion part of the study, 6 arms defined by confirmed tumor types will enroll in parallel at the RP2D(s) of TNG456 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.
Interventions
DRUGTNG456
A selective PRMT5 inhibitor
DRUGabemaciclib
A kinase inhibitor
Sponsors
Tango Therapeutics, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 dose escalation (sequential) followed by phase 2 dose expansion (parallel)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a tumor with a confirmed MTAP loss * Is ≥18 years of age at the time of signature of the main study ICF * Has had progression or an inadequate response to or is intolerant of the approved standard of care therapy, no standard of care therapy exists, or the investigator has determined that treatment with the standard of care therapy is not appropriate. * Is able to swallow tablets * Adequate Organ function/reserve per local labs * Negative serum pregnancy test result at screening * Has an ECOG performance status score of 0 to 1 * Has measurable disease based on RECIST v1.1 or a confirmed glioblastoma (IDH-wildtype) with radiographic evidence of disease progression or recurrence defined by RANO 2.0. * Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score ≥70.
Exclusion criteria
* A female patient is who is pregnant or breastfeeding * Has impaired GI function or disease that may significantly alter the absorption of oral study treatment(s) * Has an active infection requiring systemic therapy * Has received prior treatment with a PRMT5 inhibitor or a MAT2A inhibitor * Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor * Clinically relevant cardiovascular disease * Has a prior or ongoing clinically significant illness may affect the safety of the patient, impair the assessment of study results or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Maximum Tolerated Dose | 21 days | To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib |
| Phase 2 Anti-neoplastic Activity Single Agent | 18 weeks | To assess the antitumor activity of TNG456 in patients with advanced or metastatic solid tumors with MTAP loss by RECIST or modified RANO criteria |
| Phase 2 Anti-neoplastic Activity Combination Treatment | 18 weeks | To assess the antitumor activity of TNG456 in combination with abemaciclib in patients with advanced or metastatic tumors with MTAP loss by RECIST or modified RANO criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Anti-neoplastic Activity Single Agent | 18 weeks | To assess preliminary evidence of antitumor activity of TNG456 in patients with advanced solid tumors with MTAP loss by RECIST or modified RANO criteria |
| Phase 1 and 2 Adverse Event Profile | 21 days | To describe the safety and tolerability profile of TNG456 as a monotherapy and in combination with abemaciclib |
| Phase 1 and 2 Concentration versus Time Curve | 16 days | Measure the area under the plasma concentration versus time curve (AUC) |
| Phase 1 and 2 Time to Achieve Maximal Plasma Concentration | 16 days | Measure the time to achieve maximal plasma concentration (Tmax) |
| Phase 1 and 2 Maximum Observed Plasma Concentration | 16 days | Measure the maximum observed plasma concentration (Cmax) |
Countries
United States
Contacts
CONTACTTab Cooney, MD
STUDY_DIRECTORTab Cooney, MD
Tango Therapeutics, Inc.
Outcome results
None listed