S095035 for Advanced Cancer

Recruiting at 11 trial locations

Overseen By Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Servier Bio-Innovation LLC

Disqualifiers: Second primary malignancy, Cardiovascular disease, Thrombosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human Phase 1, multicenter, open-label dose escalation study of S095035 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have received any systemic anticancer treatment or radiotherapy within 2 weeks before starting the trial.

What safety data exists for the treatment S095035 in humans?

The safety of oral anticancer drugs, which may include treatments like S095035, has been evaluated in studies showing that serious adverse effects (SAEs) such as gastrointestinal toxicity can occur, often early in treatment. Managing these side effects is important, and measures against gastrointestinal issues are particularly emphasized. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors missing the MTAP gene, who've tried at least one treatment without success and have no other standard options left. They should be in relatively good health (ECOG PS 0-1), expect to live at least three more months, can use effective birth control, and are willing to provide tumor tissue samples.

Inclusion Criteria

Estimated life expectancy ≥3 months

Participants able to comply with highly effective method of birth control requirements

I am fully active or can carry out light work.

Exclusion Criteria

Have a known history of Gilbert's syndrome

I have an active liver or biliary disease.

I have active cancer spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of S095035 to determine the optimal dose

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 2 years

Treatment Details

Interventions

• S095035

Trial Overview The study tests S095035, an oral drug designed to inhibit a specific enzyme linked with cancer growth in patients whose tumors lack the MTAP gene. It's an early-stage trial where researchers gradually increase doses to find safe levels.

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Servier Bio-Innovation LLC

Lead Sponsor

Trials

9

Recruited

670+

Institut de Recherches Internationales Servier

Collaborator

Trials

91

Recruited

67,100+

Findings from Research

A study involving 63 cancer outpatients treated with oral anticancer agents revealed that 74.6% reported at least one high-level symptom, highlighting the prevalence of adverse events in this population.

The most commonly reported symptoms included fatigue, psychological disorders, and general pain, indicating that patient-reported outcomes (PROs) are effective for identifying significant side effects and can be integrated into routine oncology care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Patient Reported Outcomes (PROs) in Outpatients Taking Oral Anticancer Drugs Included in the Real-Life Oncoral Program. Collomb, B., Dubromel, A., Caffin, AG., et al.[2022]

Checkpoint inhibitors, which target CTLA-4, PD-1, and PD-L1, have shown significant effectiveness in improving survival rates for patients with various solid and hematologic cancers, highlighting their potential as powerful cancer treatments.

Despite their efficacy, these therapies can lead to severe adverse events like fatigue, rash, and autoimmune reactions, which may require careful management, including the use of steroids that can compromise the overall anti-tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-oncology: a narrative review of gastrointestinal and hepatic toxicities. Boussios, S., Sheriff, M., Rassy, E., et al.[2021]

In a study of 1,832 patients receiving outpatient oral anticancer drugs, serious adverse effects (SAEs) were reported in 2.8% of cases, with gastrointestinal toxicity being the most common issue.

SAEs typically occurred early in treatment, with a median onset of 32 days, highlighting the need for proactive management of gastrointestinal side effects when administering these chemotherapeutic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of serious adverse events and safety evaluation of oral anticancer drug treatment in Japan: A retrospective study. Kawasumi, K., Kujirai, A., Matsui, R., et al.[2020]

Combining anti-PD-1 or anti-PD-L1 immunotherapy with platinum-based chemotherapy significantly improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), based on a systematic review of 9 randomized studies.

While immune-mediated adverse events (AEs) and infusion reactions were more common with the combination therapy, there were no unexpected toxicities, indicating that the treatment is generally safe and manageable with appropriate monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. Hoffner, B., Leighl, NB., Davies, M.[2020]

Out of 236 Individual Case Safety Reports (ICSRs) analyzed, only 18 (7.6%) were classified as off-label cases, indicating a low incidence of off-label use of antineoplastic drugs in pediatric patients, primarily related to therapeutic indications.

Among the off-label cases, 29 adverse drug reactions (ADRs) were reported, with common reactions including diarrhea and neutropenia, suggesting that while off-label use is limited, it can still lead to significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System. Mascolo, A., Scavone, C., Bertini, M., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Assessment of Patient Reported Outcomes (PROs) in Outpatients Taking Oral Anticancer Drugs Included in the Real-Life Oncoral Program. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Immuno-oncology: a narrative review of gastrointestinal and hepatic toxicities. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Survey of serious adverse events and safety evaluation of oral anticancer drug treatment in Japan: A retrospective study. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System. [2022]