A Phase 1/2, Open-label, Multicenter Clinical Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Antineoplastic Activity of S095035 (MAT2A Inhibitor) as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Homozygous Deletion of MTAP

Plain English Summary

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP is a Phase 2 clinical trial sponsored by Servier Bio-Innovation LLC studying MTAP-deleted Solid Tumors. This trial tests a new drug (S095035) alone or with another drug (TNG462) to see if it's safe and effective. It's for adults with advanced or metastatic solid tumors that have a specific genetic change called MTAP homozygous deletion. Participation involves taking study drugs by mouth and regular medical check-ups, including potential tumor biopsies. Standard treatments for these advanced cancers may have failed or are not available. The trial aims to enroll 342 participants.

Official Summary

This is a first-in-human Phase 1/2, multicenter, open-label study of S095035 as single-agent, or in combination with TNG462 in adult participants with advanced or metastatic solid tumors with homozygous deletion of MTAP who have failed to respond to or have progressed after at least 1 prior treatment regimen, and for whom additional effective standard treatment is not available. S095035 is an oral methionine adenosyltransferase 2A \[MAT2A\] inhibitor. TNG462 is a protein arginine N-methyltransferase 5 \[PRMT5\] inhibitor.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults (18+) with advanced or metastatic solid tumors that have a confirmed MTAP homozygous deletion. Patients must have had at least one prior treatment for their advanced cancer and have a life expectancy of at least 3 months. Individuals with certain other active cancers or medical conditions that could interfere with the study drug may not be eligible. Participants must be able to use effective birth control. This trial is studying MTAP-deleted Solid Tumors, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the drugs are (side effects and dose-limiting toxicities) and how well they shrink tumors (objective response rate). The specific primary outcome measures are: Dose limiting toxicities (DLTs) (Through cycle 1 (each cycle is 28 days)); Total number of adverse events (AEs) (Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years); Total number of serious adverse events (SAEs) (Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years); Objective response rate (ORR) (Through the end of the study (approximately 5 years)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a gap in treatment for advanced solid tumors with a specific genetic vulnerability (MTAP deletion), offering a new therapeutic approach. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets MTAP-deleted Solid Tumors, where improved treatment options are needed.

Investor Insight

This trial targets a specific genetic alteration found in various cancers, potentially opening a new treatment avenue and indicating a focus on precision medicine for a niche but significant patient p Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the study drugs, potential side effects, and what it means to have an MTAP deletion in your tumor. Be prepared for regular clinic visits for assessments, drug administration, and possibly tumor biopsies. Understand that this is an open-label study, meaning both you and the study team will know which treatment you are receiving. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 342 participants

Interventions

• DRUG: S095035 — S095035 will be taken orally every day in 28-day cycles.
• DRUG: TNG462 — TNG462 will be taken orally every day in 28-day cycles.

Primary Outcomes

• Dose limiting toxicities (DLTs) (Through cycle 1 (each cycle is 28 days))
• Total number of adverse events (AEs) (Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years)
• Total number of serious adverse events (SAEs) (Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years)
• Objective response rate (ORR) (Through the end of the study (approximately 5 years))

Secondary Outcomes

• Area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t) (Through the last dose of study treatment (approximately 5 years))
• AUC from 0 to infinity (AUC0-∞) (Through the last dose of study treatment (approximately 5 years))
• AUC over 1 dosing interval at steady state (AUCtau,ss) (Through the last dose of study treatment (approximately 5 years))
• Time to maximum concentration (Tmax) (Through the last dose of study treatment (approximately 5 years))
• Maximum concentration (Cmax) (Through the last dose of study treatment (approximately 5 years))

Full Eligibility Criteria

Inclusion Criteria:

* Estimated life expectancy ≥3 months.
* ECOG PS 0-1
* Participants able to comply with highly effective method of birth control requirements.
* Participants with histologically confirmed advanced or metastatic solid tumor's (excluding central nervous system tumors other than IDHwt glioblastoma), with measurable disease as per RECIST 1.1 or RANO 2.0 criteria for participants with IDHwt glioblastoma, that have progressed after at least one prior treatment regimen given for advanced/metastatic disease, and for whom additional effective standard therapy is not available. Patients in China with IDHwt glioblastoma will not be included.
* Participants with pre-existing documented MTAP homozygous gene deletion in their tumor tissue, determined using a next generation sequencing in vitro diagnostic test prior to screening.
* Phase 1 only - Participants (except IDHwt glioblastoma) willing to undergo paired fresh biopsy (pre-treatment and on-treatment) procedure. Exceptions may be made for feasibility and safety concerns. IDHwt glioblastoma must provide archival tissue from most recent surgery or biopsy.
* Adequate organ functions.
* Phase 2 only - Participants in dose expansion, except those with IDHwt glioblastoma, must provide newly collected tumor biopsies at screening. If not medically feasible archival tissue may be used, provided it was collected within 3 months before study entry and no treatment has been received since the most recent biopsy.
* Phase 2 only - Participants with IDHwt glioblastoma must provide archival tissue from their most recent surgery or biopsy, collected before screening.
* Phase 2 only - Participants in China who are to be considered for enrollment in the single agent dose expansion Arms and who have a pre-existing, documented cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous gene deletion in their tumor tissue (confirmed by an NGS IVD test), but do not have homozygous MTAP deletion reported, will need to be pre-screened to confirm homozygous MTAP deletion. Pre screening for homozygous MTAP deletion will be conducted using a central NGS IVD test using an archival tumor tissue, preferably the most recent and not older than 3 years.
* Phase 2 Arm 1a only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with homozygous deletion of MTAP, with measurable disease as per RECIST version 1.1, who have progressed or experienced disease recurrence during or after at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 1b only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced BTC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 1c only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 1d only - Participants with any other locally advanced or metastatic malignancies with homozygous deletion of MTAP, who have received and progressed of experienced recurrence during or after receiving at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 2a only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced BTC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after receiving at least 1 prior line of standard-of care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 2b only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced gastroesophageal cancer with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after receiving at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 2c only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after receiving at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.

Exclusion Criteria:

* Inability to take an orally administered drug, or medical disorder or prior surgical resection that may affect the absorption of the study drug.
* Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Spo

Trial Locations

• University of California Los Angeles, Los Angeles, California, United States
• University of California, San Francisco (Ucsf) School of Medicine, San Francisco, California, United States
• Lake Mary Cancer Center - Florida Cancer Specialists & Research Institute, Lake Mary, Florida, United States
• Community Health Network, Indianapolis, Indiana, United States
• Dana Farber Cancer Institue, Boston, Massachusetts, United States
• Duke University School of Medicine, Durham, North Carolina, United States
• Taylor Cancer Research Center, Maumee, Ohio, United States
• SCRI Oncology Partners, Nashville, Tennessee, United States
• NEXT Oncology, Austin, Texas, United States
• Scientia Clinical Research, Randwick, New South Wales, Australia
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Solid Tumors
• Metastatic Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• Bile Duct Cancer (BTC)
• Pancreatic Ductal Adenocarcinoma (PDAC)
• Gastroesophageal Cancer
• Glioblastoma
• Cancer Genomics
• Targeted Therapy
• Oncology

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