FAZ053 + PDR001 for Cancer

No longer recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Cytotoxic, Immunosuppressive, Steroids, others

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, FAZ053, alone or with another drug, PDR001, to determine their safety and effectiveness against advanced solid tumors. The goal is to assess whether these drugs can help the immune system fight cancer by targeting proteins that typically inhibit it. Suitable candidates for this trial have advanced solid tumors that have worsened despite other treatments or have no other treatment options available. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some treatments. If you're on cytotoxic or targeted cancer drugs, you need to stop them 3 weeks before starting the trial. If you've had certain antibodies or immunotherapies, a 6-week washout is needed. Check with the trial team for specifics about your medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that FAZ053, when used alone, is generally well-tolerated by patients. In earlier studies, about 52.7% of patients taking only FAZ053 reported some side effects, but these were manageable and did not cause major problems for most people.

When combined with PDR001, both drugs work together to enhance the body's immune response against tumors. While effective, this combination may cause immune-related side effects. These side effects can sometimes persist but are part of the drugs' mechanism in fighting cancer.

As this is an early-phase study, the main goal is to closely monitor safety and how the treatment interacts with the body. This ensures safety for patients before advancing to the next research stages. Prospective participants can consider these findings to understand what past participants have experienced. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about FAZ053 and PDR001 because they offer a new way to tackle cancer. Unlike traditional treatments like chemotherapy, which attack rapidly dividing cells indiscriminately, FAZ053 is designed to target specific proteins involved in immune checkpoints, potentially unleashing the body's immune system to fight cancer more effectively. PDR001 works by blocking a protein called PD-1, also involved in immune regulation, which may help the immune system recognize and destroy cancer cells. This combination could provide a more precise attack on cancer cells with potentially fewer side effects than conventional treatments.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that FAZ053 may help control certain tumors, such as alveolar soft part sarcoma (ASPS) and chordoma. It blocks a process that typically allows cancer cells to evade the immune system, thereby activating T-cells, which can attack tumors.

In this trial, participants will be assigned to different treatment arms. One arm will receive FAZ053 as a single agent. Studies have shown that most patients tolerated FAZ053 well, experiencing no severe side effects. Another arm will receive a combination of FAZ053 with PDR001, a drug that aids the immune system in fighting cancer. Early results suggest this combination is safe and functions similarly to other drugs already benefiting many cancer patients. These findings support the potential effectiveness of FAZ053, alone or with PDR001, in treating advanced solid tumors. ^{1 3 4 5 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including breast cancer and rare cancers like chordoma and alveolar soft part sarcoma. Participants may have had previous treatments but must have progressed despite those or have no standard treatment options available. They should be able to undergo a tumor biopsy and not be on chronic steroids or immunosuppressive therapy, nor should they have untreated brain metastases or severe allergies to monoclonal antibodies.

Inclusion Criteria

I have advanced cancer with a measurable tumor and may have had immunotherapy but not anti-PD-L1 treatment.

I can take care of myself but might not be able to do heavy physical work.

I have advanced cancer with no standard treatment left or that has not responded to treatment.

Exclusion Criteria

I do not have active autoimmune diseases except for vitiligo, stable thyroid issues, or mild psoriasis.

I haven't taken cancer drugs or immunotherapy for the past 3 to 6 weeks.

I do not have active brain metastases needing immediate treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation part of FAZ053 as single agent and in combination with PDR001 to determine safety and tolerability

21-42 days

Visits every 3 weeks

Dose Expansion

Dose expansion part of FAZ053 as single agent to further evaluate safety and antitumor activity

Up to 41 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 46 months

What Are the Treatments Tested in This Trial?

Interventions

• FAZ053
• PDR001

Trial Overview The study tests FAZ053 alone and combined with PDR001 in patients with advanced malignancies. It aims to evaluate the safety, dosage levels, how the body processes these drugs, their effects on tumors by activating immune responses against cancer cells, and overall antitumor activity.

How Is the Trial Designed?

Group I: FAZ053 single agent Experimental Treatment 1 Intervention

Group II: FAZ053 + PDR001 Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

A systematic review of 161 studies involving 17,197 patients revealed that combination therapies with PD-1 or PD-L1 inhibitors have high incidences of treatment-related adverse events, with chemotherapy combinations showing the highest overall incidence at 97.7%.

The most common all-grade adverse events across these therapies included anemia and fatigue, while grade 3 or higher adverse events were primarily neutropenia and hypertension, providing crucial safety information for clinicians managing cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis. Zhou, X., Yao, Z., Bai, H., et al.[2021]

A novel PD-L1-binding affibody (M1) was developed using mRNA display, demonstrating low nanomolar affinity for both human and mouse PD-L1, which is crucial for potential diagnostic applications.

The M1 affibody effectively inhibited PD-L1:PD-1 signaling in a cell-based assay and showed significant tumor uptake in vivo, indicating its potential as a molecular imaging probe in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directed Evolution of PD-L1-Targeted Affibodies by mRNA Display. Grindel, BJ., Engel, BJ., Ong, JN., et al.[2023]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(25)00920-2/fulltext

First-in-human study of FAZ053, an anti-programmed death ... Conclusion. FAZ053 monotherapy was well tolerated and effective in maintaining disease control in various tumors including ASPS and chordoma. ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40381383/

First-in-human study of FAZ053, an anti-programmed death ... Conclusion: FAZ053 monotherapy was well tolerated and effective in maintaining disease control in various tumors including ASPS and chordoma. The anticipated ...

3. researchgate.net researchgate.net/publication/391857495_First-in-human_study_of_FAZ053_an_anti-programmed_death-ligand_1_anti-PD-L1_monoclonal_antibody_alone_and_in_combination_with_spartalizumab_in_patients_with_advanced_malignancies

First-in-human study of FAZ053, an anti-programmed death ... Results Of the 154 patients treated, 49 (52.7%) patients receiving FAZ053 monotherapy experienced at least one treatment-related adverse event ...

4. cris.tau.ac.il cris.tau.ac.il/en/publications/first-in-human-study-of-faz053-an-anti-programmed-death-ligand-1-

First-in-human study of FAZ053, an anti-programmed death ... Results: Of the 154 patients treated, 49 (52.7%) patients receiving FAZ053 monotherapy experienced at least one treatment-related adverse event (TRAE), of ...

5. immuno-oncologynews.com immuno-oncologynews.com/faz053/

FAZ053 By inhibiting this interaction, FAZ053 enhances the activation of T-cell-mediated anti-tumor response and renders cancer cells less able to evade that response.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12146532/

First-in-human study of FAZ053, an anti-programmed death ... This study assessed the safety, tolerability, and preliminary efficacy of FAZ053 monotherapy and in combination with spartalizumab in patients with advanced ...