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Pancrelipase

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MRTX1719 RP2D administered to separate cohorts of patients with selected solid tumor malignancies with MTAP homozygous deletion to include the following: Mesothelioma, Pancreatic Adenocarcinoma, NSCLC, Malignant Peripheral Nerve Sheath Tumor, Other Solid Tumors

MRTX1719

BMS Study Connect Contact Center www.BMSStudyConnect.com

www.BMSStudyConnect.com NCT05245500 14 sites

Mayo Clinic

Research site

Bristol-Myers Squibb, MD

This is a Phase 1/2, open-label, multicenter, study of the safety, tolerability, PK, PD, and anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene.

This first-in-human clinical trial will begin with an exploration of MRTX1719 dose and regimen. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure sufficient safety experience, PK information, compare food effect and relative bioavailability between capsules and tablets, and early evidence of clinical activity are available to recommend Phase 2 regimens. In Phase 2, separate cohorts of patients by histological diagnosis and/or baseline characteristics will be evaluated for the clinical activity and efficacy of MRTX1719.

Phase 1/2 Study of MRTX1719 in Solid Tumors With MTAP Deletion

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1719 in Patients With Advanced Solid Tumors With Homozygous MTAP Deletion

Mirati Therapeutics Inc.

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

Paclitaxel

Gemcitabine

Docetaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

AG-270 will be administered on Days 1 to 28 of each 28-day cycle. Treatment will continue until disease progression or unacceptable toxicity.

AG-270 will be administered daily, starting 1 week prior to docetaxel infusion. Starting on Cycle 1 Day 1, docetaxel (by intravenous infusion \[IV\]) will be administered once during each 21-day cycle. Treatment with AG-270 and docetaxel will continue until disease progression or unacceptable toxicity.

AG-270 will be administered daily, starting 1 week prior to nab-paclitaxel and gemcitabine infusion. Starting on Cycle 1 Day 1, nab-paclitaxel and gemcitabine IV will be administered on Days 1,8, and 15 during each 28-day cycle. Treatment with AG-270, nab-paclitaxel, and gemcitabine will continue until disease progression or unacceptable toxicity.

AG-270, orally, once or twice daily, on Days 1 through 28 of each 28-day cycle, until disease progression or unacceptable toxicity.

AG-270

AG-270, orally, once or twice daily, for 1 week prior to the first dose of docetaxel. Thereafter, AG-270 continues to be given daily, on Days 1 through 21 of each 21-day cycle, until disease progression or unacceptable toxicity.

AG-270, orally, once or twice daily for 1 week prior to the first doses of nab-paclitaxel and gemcitabine. Thereafter, AG-270 continues to be given daily on Days 1 through 28 of each 28-day cycle, until disease progression or unacceptable toxicity.

Docetaxel, IV, once during each 21-day cycle, until disease progression or unacceptable toxicity.

docetaxel

Nab-paclitaxel, IV, on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.

nab-paclitaxel

Gemcitabine, IV, on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.

gemcitabine

This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of AG-270 in participants with advanced solid tumors or lymphoma with homozygous MTAP deletion.

The purpose of this Phase 1, multicenter, open-label study is to determine the maximum tolerated dose (MTD) of AG-270, administered as a single agent or in combination with taxane-based chemotherapy, and to characterize its dose-limiting toxicities (DLTs) when given daily by mouth to participants with advanced solid tumors or lymphoma with homozygous deletion of methylthioadenosine phosphorylase (MTAP).

In each arm of the study, successive cohorts of participants will receive increasing oral doses of AG-270 to determine the MTD, the dose with maximum pharmacologic activity or the maximum feasible dose, as a single agent and in combination with taxane-based chemotherapy. In the subsequent dose-expansion parts of the study, additional participants in each treatment arm will be treated at the MTD (or one of the described alternative doses) to further characterize that dose's safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and to detect preliminary evidence of anti-tumor activity.

Study of AG-270 in Participants With Advanced Solid Tumors or Lymphoma With MTAP Loss

A Phase 1 Study of AG-270 in the Treatment of Subjects With Advanced Solid Tumors or Lymphoma With Homozygous Deletion of MTAP

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

* used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Institut de Recherches Internationales Servier

Cholangiocarcinoma

Glioblastoma

Bile Duct Cancer

Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD

Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D

Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D

Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG908 at the identified RP2D

Participants with MTAP-deleted sarcoma (soft tissue and bone) will receive TNG908 at the identified RP2D

Participants with other MTAP-deleted solid tumors will receive TNG908 at the identified RP2D

Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D

TNG908, a selective PRMT5 inhibitor, will be administered orally

TNG908

Tango Clinical Trials

Tim Cloughesy, MD

Nicholas Butowski, MD

Roger Stupp, MD

Ibiayi Dagogo-Jack, MD

Ugonma Chukwueke, MD

Angela Hirbe, MD, PhD

Mrinal Gounder, MD

David Spigel, MD

Jordi Rodon Ahnert, MD

Alex Spira, MD

Philippe Cassier, MD

Ludovic Doucet, MD

Capucine Baldini, MD

Ellen Hooper, MD

This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG908, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 192 participants.

This is a Phase 1/2 multi-center, open label study in solid tumor patients (including glioblastoma) who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG908 in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 6 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D of TNG908. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 6 arms (parallel)

Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors

A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG908 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors

To determine the MTD and dosing schedule of TNG908

To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1 or modified RANO criteria

To assess preliminary evidence of anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1or modified RANO criteria

To describe the safety and tolerability profile of TNG908 by frequency and severity of AEs

Area under the plasma concentration versus time curve (AUC)

Time to achieve maximal plasma concentration (Tmax)

Maximum observed plasma concentration (Cmax)

Apparent total plasma clearance when dosed orally (CL/F)

Apparent volume of distribution when dosed orally (Vz/F)

SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG908

Tango Therapeutics, Inc.

Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 to estimate the MTD

Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D

Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D

Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D

Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D

Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D

TNG462, a selective PRMT5 inhibitor, will be administered orally

TNG462

Christopher Chen

Jose Lutzky, MD

Candace Haddox, MD

Amy Weise, DO

Salman Punekar, MD

Ignacio Garrido-Iaguna, MD, PhD

Irene Brana, MD

Victor Moreno Garcia, MD

Emiliano Calvo Aller, MD

This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 159 participants.

This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG462 in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 5 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D of TNG462. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 5 arms (parallel)

Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors

To determine the maximum tolerated dose (MTD) of TNG462

To determine the dosing schedule of TNG462

To assess anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or mRECIST v1.1

To assess preliminary evidence of anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or mRECIST v1.1

To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs

Measure the area under the plasma concentration versus time curve (AUC)

Measure the time to achieve maximal plasma concentration (Tmax)

Measure the maximum observed plasma concentration (Cmax)

Determine the terminal elimination half-life (t1/2)

Determine the apparent total plasma clearance when dosed orally (CL/F)

Determine the apparent volume of distribution when dosed orally (Vz/F)

SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1/2 Study of MRTX1719 in Solid Tumors With MTAP Deletion	NCT05245500	Mesothelioma Non Small Cell ... Malignant Perip... Solid Tumor Pancreatic Aden... Advanced Solid ...	MRTX1719	18 Years -	Mirati Therapeutics Inc.
Study of AG-270 in Participants With Advanced Solid Tumors or Lymphoma With MTAP Loss	NCT03435250	Advanced Solid ... Lymphoma	AG-270 AG-270 AG-270 docetaxel nab-paclitaxel gemcitabine	18 Years -	Servier
Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors	NCT05275478	Locally Advance...	TNG908	18 Years -	Tango Therapeutics, Inc.
Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors	NCT05732831	Locally Advance...	TNG462	18 Years -	Tango Therapeutics, Inc.
Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion	NCT04794699	Solid Tumor	IDE397 Docetaxel Paclitaxel Sacituzumab gov...	18 Years -	IDEAYA Biosciences
Study of AG-270 in Participants With Advanced Solid Tumors or Lymphoma With MTAP Loss	NCT03435250	Advanced Solid ... Lymphoma	AG-270 AG-270 AG-270 docetaxel nab-paclitaxel gemcitabine	18 Years -	Servier
S095035 in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of the Methylthioadenosine Phosphorylase (MTAP) Gene	NCT06188702	MTAP-deleted So...	S095035	18 Years -	Servier

Spots Global Cancer Trial Database for mtap deletion