40 Participants Needed

DFF332 + Combination Therapy for Renal Cell Carcinoma

Recruiting at 22 trial locations
NP
Overseen ByNovartis Pharmaceuticals
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called DFF332 in patients with advanced kidney cancer and other cancers with certain genetic mutations. The drug works by blocking a protein that helps the cancer grow.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain cancer treatments before starting the study. Specifically, you must not have had chemotherapy, biological therapy, or certain other cancer treatments within a few weeks before the trial begins. The protocol does not specify about other non-cancer medications, so it's best to discuss your current medications with the trial team.

What makes the drug DFF332 unique for treating renal cell carcinoma?

The drug DFF332 is unique for treating renal cell carcinoma because it is part of a combination therapy approach, which is a newer strategy in cancer treatment that aims to overcome resistance and improve survival by using multiple active agents together. This approach is different from traditional single-agent therapies and reflects the evolving treatment landscape for this condition.12345

What data supports the effectiveness of the drug combination DFF332, NIR178, PDR001, and RAD001 for renal cell carcinoma?

Research shows that combination therapies targeting immune checkpoints and specific growth factors have improved outcomes in advanced renal cell carcinoma, with some drugs like everolimus (similar to RAD001) extending survival in certain patients. This suggests that combining active agents, like those in the trial, could potentially enhance treatment effectiveness.12567

Who Is on the Research Team?

NP

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with advanced clear cell renal cancer (ccRCC) who've tried all standard treatments, including PD-1/L1 inhibitors and VEGF therapies. It's also open to those with certain genetic mutations or syndromes related to other cancers, as long as they have no remaining standard treatment options. People can't join if they have heart issues, uncontrolled illnesses like high blood pressure or infections, recent major surgery, or are pregnant.

Inclusion Criteria

I am 12 years old or older.
My kidney cancer has spread, can't be surgically removed, and has worsened after all standard treatments.
I am 16 or older and mostly able to care for myself.
See 6 more

Exclusion Criteria

Other protocol-defined inclusion/exclusion criteria may apply
Pregnant or nursing (lactating) women
I have been treated with a HIF2α inhibitor before.
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Initial evaluation of DFF332 as a single agent, followed by combination with Everolimus or Spartalizumab plus Taminadenant after two dose levels of single agent have been evaluated

28 days

Dose Expansion

Expansion of single agent and combination arms to further assess safety and efficacy in specific patient groups

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

  • DFF332
  • NIR178
  • PDR001
  • RAD001
Trial Overview The study tests DFF332 alone and combined with Everolimus (RAD001), Spartalizumab (PDR001), and Taminadenant (NIR178). These drugs target different aspects of cancer growth: HIF2α protein by DFF332; mTOR pathway by RAD001; immune checkpoints by PDR001; and adenosine A2A receptors by NIR178.
How Is the Trial Designed?
7Treatment groups
Experimental Treatment
Group I: Arm 3a Dose Expansion DFF332 + Spartalizumab + Taminadenant in ccRCCExperimental Treatment3 Interventions
Group II: Arm 3 Dose Escalation DFF332 + Spartalizumab + TaminadenantExperimental Treatment3 Interventions
Group III: Arm 2a Dose Expansion DFF332 + Everolimus in ccRCCExperimental Treatment2 Interventions
Group IV: Arm 2 Dose Escalation DFF332 + EverolimusExperimental Treatment2 Interventions
Group V: Arm 1b Dose Expansion DFF332 in HIF stabilizing malignanciesExperimental Treatment1 Intervention
Group VI: Arm 1a Dose Expansion DFF332 in ccRCCExperimental Treatment1 Intervention
Group VII: Arm 1 Dose Escalation DFF332Experimental Treatment1 Intervention

Find a Clinic Near You

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 profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a phase III trial, the multi-kinase inhibitor sorafenib significantly improved median progression-free survival in advanced renal cell carcinoma patients, doubling it from 12 weeks to 24 weeks, with a hazard ratio of 0.44.
Sorafenib also showed a 39% improvement in overall survival and a 10% investigator-assessed response rate, highlighting that many patients experienced clinical benefits beyond traditional tumor regression metrics.
Emerging efficacy endpoints for targeted therapies in advanced renal cell carcinoma.Gore, ME., Escudier, B.[2018]
Combination therapies targeting immune checkpoints and vascular endothelial growth factor receptors have significantly improved outcomes for patients with metastatic renal cell carcinoma, leading to durable disease control and prolonged overall survival.
The evolving understanding of the disease at genomic and immunologic levels has resulted in marked improvements in survival rates, making combination approaches the standard of care for first-line treatment, although careful study design is essential for accurate outcome estimation.
Treatment Selection in First-line Metastatic Renal Cell Carcinoma-The Contemporary Treatment Paradigm in the Age of Combination Therapy: A Review.Navani, V., Heng, DYC.[2022]

Citations

Preclinical efficacy of dual mTORC1/2 inhibitor AZD8055 in renal cell carcinoma harboring a TFE3 gene fusion. [2021]
Emerging efficacy endpoints for targeted therapies in advanced renal cell carcinoma. [2018]
Treatment Selection in First-line Metastatic Renal Cell Carcinoma-The Contemporary Treatment Paradigm in the Age of Combination Therapy: A Review. [2022]
Combination systemic therapy for advanced renal cell carcinoma. [2009]
Analysis of efficacy of sorafenib combined with vascular endothelial growth factor inhibitor on renal cell carcinoma. [2020]
Evolving Treatment Paradigm in Metastatic Renal Cell Carcinoma. [2019]
7.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Targeted therapies in the treatment of advanced renal cell carcinoma. [2021]
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