Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).

Summary

The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deleted thoracic tumors. The study also aims to determine the safety profile of Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted thoracic tumors.

Eligibility

Inclusion Criteria

Subprotocol A, B, and C

* Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
* Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before Anvumetostat dosing.
* Homozygous MTAP-deletion
* Able to swallow and retain PO administered study treatment.
* Disease measurable as defined by RECIST v1.1.

Subprotocol A - Histologically or cytologically confirmed diagnosis of NSCLC.

Arm A (Anvumetostat + carboplatin + paclitaxel + pembrolizumab):

\- Predominantly squamous histology.

Arm B (Anvumetostat + carboplatin + pemetrexed + pembrolizumab):

\- Predominantly non-squamous histology.

Arm C (Anvumetostat + pembrolizumab):

\- PD-L1 positive.

Subprotocol B - Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation.

Subprotocol C

* Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases.
* Brain lesion meeting RANO-BM criteria for measurable disease.

Exclusion Criteria

Subprotocol A, B, and C

* Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
* Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
* History of solid organ transplant.
* Major surgery within 28 days of first dose of Anvumetostat.
* Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
* Radiation therapy within 28 days of first dose.

Subprotocol A

\- Autoimmune disease or immunodeficiency disease as defined in the protocol'

Conditions4

Interventions7

Locations26 sites

Find trials near these locations

Related trials

• A Study Evaluating Anvumetostat in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103) — Amgen
• A Phase I/II Study of CS2009 in Participants With Advanced Solid Tumors — CStone Pharmaceuticals
• A Phase Ib Clinical Study on the Safety and Efficacy of HC010 Combinations in Advanced Solid Tumors — HC Biopharma Inc.
• A Phase Ib/II Study Of JS015 Combination Therapy in Advanced Solid Tumors — Shanghai Junshi Bioscience Co., Ltd.
• A Randomized, Open-label, Multi-center Phase III Study Comparing the Efficacy of Oral Chemotherapy Combined With Trastuzumab Versus Paclitaxel Combined With Trastuzumab in the Adjuvant Treatment of HER2-positive, Lymph Node-negative Early Breast Cancer Patients(ORCHID-PLUS) — Fudan University
• A Safety and Efficacy Study of Bevacizumab, Paclitaxel, Carboplatin Compared to Avastin® in Non-Small Cell Lung Cancer — Mabscale, LLC
• A Study of B013 in Combination With Paclitaxel in Patients With Platinum-resistant Recurrent Ovarian Cancer. — Shanghai Jiaolian Drug Research and Development Co., Ltd
• A Study of Dostarlimab in Combination With Carboplatin-paclitaxel in Chinese Participants With Primary Advanced or Recurrent Endometrial Cancer (EC) — GlaxoSmithKline

Browse More Trials