QEQ278 for Cancer

Recruiting at 16 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Chronic steroids, Immunosuppressives

Disqualifiers: Autoimmune, Interstitial lung, Cardiac, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic chronic steroid therapy or any immunosuppressive therapy, you may need to stop these at least 7 days before starting the study treatment.

What safety data exists for QEQ278 or similar treatments in humans?

Molecular target anticancer drugs, which may include treatments like QEQ278, have been shown to increase the risk of serious adverse events (SAEs) and fatal adverse events (FAEs) compared to placebo. In a large analysis, the risk of SAEs was 1.57 times higher and FAEs 1.51 times higher for these drugs, indicating a need for careful monitoring of safety in patients. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new drug called QEQ278 in adults with advanced cancers that are hard to treat. Researchers aim to find out if the drug is safe and if it can help shrink tumors.

Eligibility Criteria

Adults over 18 with advanced cancers like non-small cell lung, renal cell, esophageal squamous cell carcinoma, or HPV-related head and neck cancer. Participants must have measurable disease, be unresponsive to standard treatments or ineligible for them, and willing to undergo tumor biopsies. Exclusions include those with tuberculosis history, poor bone marrow function, serious infections including COVID-19, significant cardiac issues or a history of severe reactions to anti-PD-1 therapy.

Inclusion Criteria

I have been diagnosed with esophageal squamous cell carcinoma.

I am willing and able to have a tumor biopsy as per my hospital's rules.

My cancer in the head or neck is linked to HPV.

Exclusion Criteria

I have never had severe lung inflammation.

I do not have any serious uncontrolled infections.

I have heart problems or risk factors for heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients with various cancers are treated with QEQ278 until the maximum tolerated dose is reached or a lower recommended dose is established

24 weeks

Regular visits for dose adjustments and monitoring

Dose Expansion

After establishing the maximum tolerated dose, further patients are treated to assess safety and efficacy

24 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 months

Treatment Details

Interventions

• QEQ278

Trial Overview The trial is testing the safety and effects of QEQ278 when given intravenously to patients with certain advanced solid tumors. It will assess how the body processes the drug (pharmacokinetics), its impact on the body (pharmacodynamics), tolerability at different doses and preliminary effectiveness in shrinking tumors.

Participant Groups

Group I: Part 2: Dose expansion Experimental Treatment 1 Intervention

Dose expansion with QEQ278 single agent

Group II: Part 1: Dose escalation Experimental Treatment 1 Intervention

Dose escalation with QEQ278 single agent

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 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]

The ADEStrata approach, developed in this study, allows for the stratification of tumor mutations based on adverse drug events (ADEs), specifically focusing on musculoskeletal adverse events in breast cancer patients treated with aromatase inhibitors, using data from 212 patients.

By prioritizing somatic variants linked to ADEs, the study found that this method can identify high-risk patients who may experience poor outcomes, suggesting that it could help tailor cancer therapies to improve patient safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors. Wang, C., Zimmermann, MT., Prodduturi, N., et al.[2018]

The number of post-authorization safety and effectiveness studies (PASSs/PAESs) for oncology drugs has significantly increased, from just 1 study between 2006-2010 to 47 studies from 2016-2020, indicating a growing emphasis on real-world evidence for drug safety and effectiveness.

Most of these studies (64.1%) focused on safety/risk assessment, particularly regarding adverse events, while effectiveness studies primarily aimed at measuring overall survival, highlighting the need for more comparative analyses in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulator-Requested Non-Interventional Postauthorization Safety and Effectiveness Studies for Oncology Drugs: A Systematic Review. Zhang, X., Chen, L., Bracco, OL., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

References

1. 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]

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

Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors. [2018]

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

Regulator-Requested Non-Interventional Postauthorization Safety and Effectiveness Studies for Oncology Drugs: A Systematic Review. [2022]

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

Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis. [2020]

5. England pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]