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A Phase I/II, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG456 Monotherapy and in Combination with Abemaciclib in Patients with Solid Tumors with MTAP Loss

Orthopaedics, Cancer
Cathleen Park
Anus
Bones and Joints
Brain and Nervous System
Breast
Cervix
Colon
Corpus Uteri
Esophagus
Eye and Orbit
Ill-Defined Sites
Kaposis sarcoma
Kidney
Larynx
Lip Oral Cavity and Pharynx
Liver
Lung
Melanoma skin
Mycosis Fungoides
Other Digestive Organ
Other Endocrine System
Other Female Genital
Other Male Genital
Other Respiratory and Intrathoracic Organs
Other Skin
Other Urinary
Ovary
Pancreas
Prostate
Rectum
Small Intestine
Soft Tissue
Stomach
Thyroid
Unknown Sites
Urinary Bladder

Study Description

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.

Eligibility

The subject can participate in this study if the subject:

  1. Has a tumor with a confirmed MTAP loss
  2. Is equal or greater than 18 years of age at the time of signature of the main study ICF
  3. 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.
  4. Is able to swallow tablets
  5. Has adequate organ function/reserve per local labs
  6. Negative serum pregnancy test result at screening
  7. Has an ECOG performance status score of 0 to 1
  8. 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.
  9. Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score equal or greater than 70.

The subject cannot participate in this study if the subject:

  1. is a female patient is who is pregnant or breastfeeding
  2. Has impaired GI function or disease that may significantly alter the absorption of oral study treatment(s)
  3. Has an active infection requiring systemic therapy
  4. Has received prior treatment with a PRMT5 inhibitor or a MAT2A inhibitor
  5. Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor
  6. Clinically relevant cardiovascular disease
  7. 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
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