PRS-344/S095012 for Advanced Cancer

No longer recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called PRS-344/S095012 for individuals with advanced or metastatic solid tumors, where the cancer has spread and cannot be surgically removed. The goal is to determine the safety of this treatment and how well participants can tolerate it. This trial might suit those diagnosed with such a tumor, who have tried other treatments without success, and have at least one measurable tumor. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that PRS-344/S095012 is likely to be safe for humans?

Research shows that PRS-344/S095012 targets cancer cells more effectively by boosting the immune system's response. In early lab studies, this treatment outperformed some current therapies against tumors.

Since this trial is in its first phase with humans, the main focus is on determining the drug's safety. Researchers will observe how the body processes the treatment and monitor for any side effects. Being in this early stage means they are still learning about its safety in humans.

Overall, for those considering participation, the main goal is to assess how well people tolerate the treatment and ensure its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PRS-344/S095012 for advanced cancer because it represents a novel approach to treatment. Unlike existing therapies that often target cancer cells directly, PRS-344/S095012 is designed to engage the immune system to attack tumors, potentially offering a more targeted and efficient response. This drug utilizes a unique mechanism by leveraging bispecific antibodies, which can simultaneously bind to cancer cells and immune cells, enhancing the body's natural ability to fight cancer. This innovative strategy could lead to more effective treatments with fewer side effects compared to traditional chemotherapy and radiation therapies.

What evidence suggests that PRS-344/S095012 might be an effective treatment for advanced cancer?

Research shows that PRS-344/S095012, the investigational treatment in this trial, could be promising for advanced cancers. Early lab studies demonstrated that it worked better against tumors than treatments targeting either PD-L1 or 4-1BB alone. PRS-344/S095012 boosts T-cell activity, crucial for fighting cancer, but only when cancer cells have PD-L1. This targeted approach might enhance effectiveness and reduce side effects. Although human studies provide limited information, these early results suggest it could help treat advanced solid tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Tim Demuth, MD, PhD

Principal Investigator

Pieris Pharmaceuticals

Are You a Good Fit for This Trial?

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

I can have a biopsy because I don't have previous tissue samples.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT078/761427/Abstract-CT078-Results-of-a-phase-1-first-in-human

Results of a phase 1 first-in-human study of PRS-344 ... In preclinical studies PRS-344/S095012 showed superior anti-tumor efficacy compared to monospecific anti-PD-L1 or 4-1BB antibodies. Methods ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9662934/

The PD-L1/4-1BB Bispecific Antibody–Anticalin Fusion ... Overall, these data demonstrate that PRS-344/S095012 enhances T-cell activity only in the context of PD-L1–expressing cells, as opposed to 20H4.9, whose ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05159388

A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific ... This is a first-in-human (FIH), phase 1/2, multi center, open-label, dose escalation and cohort expansion study designed to determine the safety and ...

4. clinicaltrials.eu clinicaltrials.eu/inn/prs-344/

Prs-344 – Application in Therapy and Current Clinical ... A groundbreaking clinical trial is underway to evaluate the safety and effectiveness of PRS-344/S095012, a novel drug designed to target solid tumors. This ...

5. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT077/761654/Abstract-CT077-Pharmacodynamic-characterization-of

Pharmacodynamic characterization of PRS-344/S095012, a ... ... PRS-344/S095012 (NCT05159388) in patients with advanced solid tumors. Methods: 45 patients received PRS-344/S095012 (12-80 mg IV) every 2 weeks.