FAZ053 + PDR001 for Cancer

Recruiting at 15 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

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, FAZ053, given through a vein, alone or with another drug, PDR001. It targets adults with serious cancers and works by helping the immune system attack cancer cells.

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.

What data supports the effectiveness of the drugs FAZ053 and PDR001 for cancer treatment?

The research highlights the effectiveness of anti-PD-1/PD-L1 therapies, like PDR001, in treating certain cancers, such as non-small cell lung cancer, where patients have shown significant responses. This suggests potential benefits of PDR001 in cancer treatment, although specific data on FAZ053 is not provided. ^{1 2 3 4 5}

What safety data exists for FAZ053 + PDR001 in humans?

PD-1 and PD-L1 inhibitors, like PDR001, can cause immune-related side effects, which may become long-lasting in some patients. These side effects are important to consider when evaluating the safety of these treatments in humans. ^{6 7 8 9 10}

How does the FAZ053 + PDR001 drug work differently from other cancer treatments?

The FAZ053 + PDR001 drug combination is unique because it targets the PD-1/PD-L1 immune checkpoint, which is a mechanism that tumors use to evade the immune system. This approach is different from traditional cancer treatments as it aims to reactivate the body's own immune response to fight cancer cells. ^{11 12 13 14 15}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Maintenance Therapy for ATM-Deficient Pancreatic Cancer by Multiple DNA Damage Response Interferences after Platinum-Based Chemotherapy. [2021]

3. Singapore pubmed.ncbi.nlm.nih.gov

Pathologic complete response to preoperative immunotherapy in a lung adenocarcinoma patient with bone metastasis: A case report. [2021]

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

Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Camrelizumab in different PD-L1 expression cohorts of pre-treated advanced or metastatic non-small cell lung cancer: a phase II study. [2022]

6. England 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. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Serum immune modulators associated with immune-related toxicities and efficacy of atezolizumab in patients with non-small cell lung cancer. [2023]

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

Extended Follow-Up of Chronic Immune-Related Adverse Events Following Adjuvant Anti-PD-1 Therapy for High-Risk Resected Melanoma. [2023]

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

Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC. [2021]

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

Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and anti-angiogenic therapy for solid tumors: A systematic review and meta-analysis. [2023]

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

Screening and production of an affibody inhibiting the interaction of the PD-1/PD-L1 immune checkpoint. [2020]

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

Cancer-associated fibroblasts promote PD-L1 expression in mice cancer cells via secreting CXCL5. [2020]

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

In Vitro Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action. [2020]

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

Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy. [2020]

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

Directed Evolution of PD-L1-Targeted Affibodies by mRNA Display. [2023]