PRS-344/S095012 for Advanced Cancer

Recruiting at 10 trial locations

Overseen By Onyeka Ogbonnaya

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Servier Bio-Innovation LLC

Must not be taking: 4-1BB agonists

Disqualifiers: Brain metastases, Major surgery, Tuberculosis, others

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

Compensation: Varies

Number of Visits: Unknown

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, PRS-344/S095012, in patients with advanced or metastatic solid tumors. It aims to find the safest and most effective dose.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you have recently taken certain treatments like small molecule inhibitors or chemotherapy, you may need to wait a few weeks before joining the trial.

What is known about the safety of PD-1/PD-L1 inhibitors in cancer treatment?

PD-1/PD-L1 inhibitors, used in treating advanced cancers like non-small cell lung cancer and melanoma, have shown some safety concerns. They can cause adverse events (side effects) such as immune-related reactions, with serious events occurring in a minority of patients. It's important to monitor for these side effects during treatment. ^{1 2 3 4 5}

Research Team

Tim Demuth, MD, PhD

Principal Investigator

Pieris Pharmaceuticals

Eligibility Criteria

Adults (≥18 years) with advanced or metastatic solid tumors that standard treatments can't help anymore are eligible for this trial. They must have at least one measurable tumor, be in good physical condition (ECOG 0-1), and women must use effective birth control. Patients who've had major surgery recently, unstable brain metastases, or recent other cancer therapies may not qualify.

Inclusion Criteria

Patients must have at least one measurable target lesion as per RECIST 1.1

I am 18 years old or older.

I am using effective birth control and will continue for 120 days after my last treatment.

Exclusion Criteria

I have previously been treated with 4-1BB agonists.

I haven't had certain cancer treatments in the last 3 weeks or 5 half-lives, whichever is shorter.

I haven't had certain experimental cancer treatments in the last 6 weeks or 5 half-lives, whichever is shorter.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase 1)

Participants receive escalating doses of PRS-344/S095012 to determine the optimal biological dose

6 months

Cohort Expansion (Phase 2)

Participants receive the optimal biological dose of PRS-344/S095012 to further assess safety and efficacy

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• PRS-344/S095012

Trial Overview The study is testing PRS-344/S095012, a new drug designed to treat various solid tumors. It's an early-stage trial to see how safe the drug is and what doses are tolerable when given to people whose cancers haven't responded to standard treatments.

Participant Groups

Group I: PRS-344/S095012 Experimental Treatment 1 Intervention

PRS-344/S095012

Who Is Running the Clinical Trial?

Servier Bio-Innovation LLC

Lead Sponsor

Trials

9

Recruited

670+

Pieris Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

250+

Institut de Recherches Internationales Servier

Collaborator

Trials

91

Recruited

67,100+

Institut de Recherches Internationales Servier (I.R.I.S.)

Collaborator

Trials

1

Recruited

50+

Findings from Research

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a retrospective study of 123 patients receiving FOLFOX 4 chemotherapy for advanced colorectal cancer, significant adverse reactions were reported, including hemotoxicity (52.8%), chronic sensory neuropathy (16.2%), and allergic reactions (15.4%).

Common side effects during initial treatment included appetite loss (60.1%), vomiting (19.5%), and acute sensory neuropathy (33.3%), highlighting the need for improved patient education and pharmaceutical care to manage these reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. Imada, H., Kawakami, K., Hiraoka, T., et al.[2013]

In a study of 111 melanoma patients treated with immunotherapy or targeted therapy, the majority received immunotherapy, particularly anti-PD-1 treatments, with a total of 371 adverse events (AEs) reported.

The incidence of AEs was lower in patients receiving anti-PD-1 therapy, with only 15.3% experiencing severe (grade 3 to 4) AEs, which were more common in those on targeted therapies, highlighting the need for better reporting and understanding of both known and unknown AEs in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. Aguiar, JP., Cardoso Borges, F., Murteira, R., et al.[2021]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. [2013]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery: Treatment of Brain Metastasis Without Interruption of Systemic Therapy. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. [2020]