Non Small Cell Lung CancerPhase 1/2NCT06810544
Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
A Phase 1/2 study testing TNG456 and abemaciclib in people with Non Small Cell Lung Cancer and Glioma Glioblastoma Multiforme, run by Tango Therapeutics, Inc. at 15 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Glioma Glioblastoma Multiforme, Glioma, Malignant
- What is being tested?
- TNG456 and abemaciclib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 191 participants
- Where
- 15 sitesUnited States
- Study dates
- 24 Mar 2025to 30 Sep 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Trial locations and contacts
15 sites in 1 country. Contact the study team or a site near you to ask about taking part.
15 sites in 1 country
United States15 sites, 15 recruiting
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Jia Luo, MD
- Recruiting
Northwestern Memorial Hospital
Chicago, Illinois, 60611-2908
Ditte Primdahl, MD
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Dwight Owen, MD
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
Alexander Spira, MD, PhD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Jordi Rodon, MD
- Recruiting
University of California, Irvine
Irvine, California, 92686
Cathleen Park, MD
- Recruiting
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Hani Babiker, MD
- Recruiting
University of California Los Angeles
Los Angeles, California, 90995
Timothy Cloughesy, MD
- Recruiting
NYU Langone Health
New York, New York, 10016
Salman Punekar, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 11065
Lauren Schaff, MD
- Recruiting
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905-0001
Kaushal Parikh, MD
- Recruiting
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112-5500
Howard Coleman, MD
- Recruiting
University of California at San Francisco
San Francisco, California, 94143-2202
Nicolas Butowski, MD
- Recruiting
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5452
Mitesh Borad, MD
- Recruiting
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Solmaz Sahebjam, MD
About this study
Official title: A Phase 1/2, 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
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.
Read the 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.
- Conditions
- Non Small Cell Lung Cancer, Glioma Glioblastoma Multiforme, Glioma, Malignant, Solid Tumor, Non-Small Cell Adenocarcinoma, Lung Cancer
- Being tested
- TNG456, abemaciclib
- Keywords
- MTAP, PRMT5 inhibitor, CDK 4/6, abemaciclib, Tango
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Glioblastoma, Glioma, Lung Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNG456Drug
A selective PRMT5 inhibitor
abemaciclibDrug
Also called Verzenio
A kinase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Single Agent and Combination Dose Escalation | Experimental | Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD Receives: Drug: TNG456; Drug: abemaciclib |
| NSCLC Single Agent Dose Expansion | Experimental | NSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) Receives: Drug: TNG456 |
| GBM Single Agent Dose Expansion | Experimental | GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) Receives: Drug: TNG456 |
| Tumor Agnostic Single Agent Dose Expansion | Experimental | Patients with specific solid tumor types that have a confirmed MTAP loss will receive TNG456 at the identified RP2D(s) Receives: Drug: TNG456 |
| NSCLC Combination Expansion | Experimental | NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib Receives: Drug: TNG456; Drug: abemaciclib |
| GBM Combination Expansion | Experimental | GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib Receives: Drug: TNG456; Drug: abemaciclib |
| Tumor Agnostic Combination Expansion | Experimental | Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib Receives: Drug: TNG456; Drug: abemaciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 Maximum Tolerated Dose
To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib
Measured: 21 days
Phase 2 Anti-neoplastic Activity Single Agent
To assess the antitumor activity of TNG456 in patients with advanced or metastatic solid tumors with MTAP loss by RECIST or modified RANO criteria
Measured: 18 weeks
Phase 2 Anti-neoplastic Activity Combination Treatment
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
Measured: 18 weeks
Secondary outcomes (5)
Phase 1 Anti-neoplastic Activity Single Agent
To assess preliminary evidence of antitumor activity of TNG456 in patients with advanced solid tumors with MTAP loss by RECIST or modified RANO criteria
Measured: 18 weeks
Phase 1 and 2 Adverse Event Profile
To describe the safety and tolerability profile of TNG456 as a monotherapy and in combination with abemaciclib
Measured: 21 days
Phase 1 and 2 Concentration versus Time Curve
Measure the area under the plasma concentration versus time curve (AUC)
Measured: 16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
Measure the time to achieve maximal plasma concentration (Tmax)
Measured: 16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
Measure the maximum observed plasma concentration (Cmax)
Measured: 16 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start24 Mar 2025
- Primary completion31 Mar 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase 1 dose escalation (sequential) followed by phase 2 dose expansion (parallel)
- Masking
- None (open label)
- Enrolment
- 191 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tango Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Adam Crystal, MD, PhD, Study director, Tango Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06810544
- Sponsor's protocol ID
- TNG456-C101
- Status last verified
- Apr 2026
- First submitted
- 24 Jan 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No