Carcinoma, Renal CellPhase 1NCT04895748
DFF332 as a Single Agent and in Combination With Everolimus & Immuno-Oncology Agents in Advanced/Relapsed Renal Cancer & Other Malignancies
A Phase 1 study testing DFF332, RAD001 and PDR001 in people with Carcinoma, Renal Cell, run by Novartis Pharmaceuticals at 11 sites in 7 countries.
Trial summary
This was a first in human study of DFF332, a small molecule that targets a protein called HIF2α. By acting on HIF2α, DFF332 may be able to stop the growth of certain types of cancer. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Carcinoma, Renal Cell
- What is being tested?
- DFF332, RAD001 and PDR001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 11 sitesin 7 countries
- Study dates
- 30 Nov 2021to 13 Feb 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female ≥ 18 years of age For Arm 1B: Male and female of age ≥ 12 years of age
- Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC). Disease must be measurable as determined by RECIST v1.1.
- For Arm 1B: histologically confirmed and documented malignancies in the context of the following cancer predisposing syndromes/disorders or harboring somatic mutations on one of these genes:
- Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)
- Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)
- Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome)
Show all 11Show fewer
- Malignancies with EPAS1/HIF2A mutations
- Malignancies with ELOC/TCEB1 mutations Note: Mutations must have been previously identified through local molecular assays.
- Patient with unresectable, locally advanced or metastatic ccRCC with documented disease progression following all standard of care therapy, including PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy as monotherapy or in combination.
- Escalation: No restriction on the number of prior treatments Expansion (with the exception of Arm 1B): Up to 3 prior lines of treatment for advanced/metastatic disease For Arm 1B: Patients must have either metastatic disease or locally advanced disease that is unresectable or that patients be unfit for resection or other treatment modalities. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, and have no available therapies of proven clinical benefit; or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
- For patients age ≥ 16 years: ECOG performance status ≤ 1 For patients age ≥ 12 and < 16 years: Lansky performance status ≥ 70
Who cannot join
- History of seizure disorder \& extrapyramidal (EPS) symptoms
- Impaired cardiac function or clinically significant cardiac disease, including any of the following:
- Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension
- Patients with corrected QT using the Fridericia's correction (QTcF) > 470 msec for all patients on screening ECG or congenital long QT syndrome Acute myocardial infarction or unstable angina < 3 months prior to study entry
- History of stroke or transient ischemic event requiring medical therapy
- Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
Show all 18Show fewer
- Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
- ≤ 4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.
- ≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.
- ≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin C.
- ≤ 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.
- Patients who have undergone major surgery ≤ 4 weeks prior to first dose of study treatment or who have not recovered for the surgical procedure.
- Patient previously treated with a HIF2α inhibitor.
- Uncontrolled concurrent illness including, but not limited to, ongoing active infection, uncontrolled hypertension, active peptic ulcer disease or gastritis, active bleeding diatheses, including any Patient known to have evidence of acute or chronic hepatitis B, hepatitis C, human immunodeficency virus (HIV), or a psychiatric illness/social situation that in the investigator's opinion would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion parts but not in the escalation parts.
- Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
- Presence of Grade ≥ 2 toxicity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAEv5.0), from prior cancer therapy with the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is permitted), ototoxicity, and alopecia.
- Pregnant or nursing (lactating) women
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
11 sites in 7 countries.
11 sites in 7 countries
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
City of Hope National Medical
Duarte, California, 91010
Uni Of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
Memorial Sloane Ketterin Cancer Ctr
New York, New York, 10065
WA Uni School Of Med
St Louis, Missouri, 63110
About this study
Official title: A Phase I/Ib, Open-label, Multi-center Study of DFF332 as a Single Agent and in Combination With Everolimus or IO Agents in Patients With Advanced/Relapsed ccRCC and Other Malignancies With HIF2α Stabilizing Mutations
This was a first in human study of DFF332, a small molecule that targets a protein called HIF2α. By acting on HIF2α, DFF332 may be able to stop the growth of certain types of cancer. DFF332 was planned to be tested at different doses as single agent and in combination with Everolimus (RAD001, an mTOR inhibitor), and also in combination with Spartalizumab (PDR001, an anti-PD1) plus Taminadenant (NIR178, an adenosine A2A receptor antagonist), in patients with advanced clear cell renal cell carcinoma and other malignancies with HIF stabilizing mutations.
Read the detailed description
This was a first in human (FIH), Phase I/Ib, open-label, multi-center study of DFF332 as a single agent and in combination with Everolimus or Spartalizumab plus Taminadenant in patients with advanced clear cell renal cell carcinoma and other malignancies with HIF stabilizing mutations.
The study consisted of two parts, dose escalation and dose expansion. The dose escalation part of the study initially evaluated DFF332 single agent. Dose escalation groups receiving DFF332 in combination with Everolimus or DFF332 in combination with Spartalizumab plus Taminadenant were planned to be opened after at least two dose levels of single agent DFF332 had been evaluated.
The dose expansion part of single agent included two treatment arms: Arm1A was planned to enroll ccRCC patients (age 18 yo or above) and Arm1B was planned to enroll patients with malignancies harboring HIF stabilizing mutations (age 12 yo and above). These included the following:
- Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)
- Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)
- Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome)
- Malignancies with EPAS1/HIF2A mutations
- Malignancies with ELOC/TCEB1 mutations
The expansion part of the combination therapies was planned to enroll patients with ccRCC and to include Arm2A (DFF332 with Everolimus) and Arm3A (DFF332 with Spartalizumab plus Taminadenant).
Novartis halted enrollment of study CDFF332A12101 in September 2023 due to business reasons and not due to safety concerns. The DFF332 single agent dose expansion arms and the dose escalation and expansion of the combination arms did not open.
- Conditions
- Carcinoma, Renal Cell
- Being tested
- DFF332, RAD001, PDR001, NIR178
- Keywords
- ccRCC, RCC, Kidney, DFF332, NIR178, PDR001, RAD001, Everolimus, Spartalizumab, Taminadenant, Von Hippel-Lindau Disease, Hereditary leiomyomatosis and renal cell cancer syndrome, Paraganglioma, Pheochromocytoma
- Medical subject headings
- Carcinoma, Renal Cell, von Hippel-Lindau Disease, Hereditary leiomyomatosis and renal cell cancer, Paraganglioma, Pheochromocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DFF332Drug
Hif2alpha inhibitor
RAD001Drug
Also called Everolimus
mTOR inhibitor
PDR001Drug
Also called Spartalizumab
anti-PD-1
NIR178Drug
Also called Taminadenant
Adenosine A2A antagonist receptor
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Dose Escalation DFF332 | Experimental | DFF332 Single Agent Receives: Drug: DFF332 |
| Arm 2 Dose Escalation DFF332 + Everolimus | Experimental | Combination treatment DFF332 + Everolimus. This arm did not open. Receives: Drug: DFF332; Drug: RAD001 |
| Arm 3 Dose Escalation DFF332 + Spartalizumab + Taminadenant | Experimental | Combination treatment DFF332 + Spartalizumab + Taminadenant. This arm did not open. Receives: Drug: DFF332; Drug: PDR001; Drug: NIR178 |
| Arm 1a Dose Expansion DFF332 in ccRCC | Experimental | DFF332 Single Agent in patients with ccRCC (age 18 years old and above). This arm did not open. Receives: Drug: DFF332 |
| Arm 1b Dose Expansion DFF332 in HIF stabilizing malignancies | Experimental | DFF332 Single Agent in patients with HIF stabilizing malignancies (age 12 years old and above). This arm did not open. Receives: Drug: DFF332 |
| Arm 2a Dose Expansion DFF332 + Everolimus in ccRCC | Experimental | Combination treatment DFF332 + Everolimus in patients with ccRCC (age 18 years old and above). This arm did not open. Receives: Drug: DFF332; Drug: RAD001 |
| Arm 3a Dose Expansion DFF332 + Spartalizumab + Taminadenant in ccRCC | Experimental | Combination treatment DFF332 + Spartalizumab + Taminadenant in patients with ccRCC (age 18 years old and above). This arm did not open. Receives: Drug: DFF332; Drug: PDR001; Drug: NIR178 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Number of participants with AEs/SAEs to characterize the safety and tolerability of DFF332 as a single agent, in combination with Everolimus (RAD001), and in combination with Spartalizumab (PDR001) plus Taminadenant (NIR178) in patients with advanced clear cell Renal Cell Carcinoma (ccRCC) and advanced malignancies with Hypoxia Inducible Factor (HIF) stabilizing mutations
Measured: 3 years
Number of participants with dose interruptions and dose reductions
Number of participants with dose interruptions and dose reductions to characterize the tolerability of DFF332 as a single agent, in combination with Everolimus (RAD001), and in combination with Spartalizumab (PDR001) plus Taminadenant (NIR178) in patients with advanced ccRCC and advanced malignancies with HIF stabilizing mutations.
Measured: 3 years
Dose intensity for DFF332 for dose escalation and expansion
Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
Measured: 3 years
Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 days) for DFF332 as a single agent and in combinations
Number of participants with DLTs
Measured: 28 days
Secondary outcomes (7)
Overall Response Rate (ORR)
To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1
Measured: 3 years
Best Overall Response (BOR)
To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1
Measured: 3 years
Progression Free Survival (PFS) for Recommended Dose (RD) only
To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1
Measured: 3 years
Duration of Response (DOR) for Recommended Dose (RD) Only
To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1
Measured: 3 years
Disease Control Rate (DCR)
To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1
Measured: 3 years
Maximum Concentration (Cmax) of DFF332 single agent and combination
PK parameters will be based on plasma concentration of DFF332 and Taminadenant, whole blood concentration of Everolimus, serum concentration of Spartalizumab
Measured: 3 years
Area under the concentration-time curve (AUC) of DFF332 single agent and combination
PK parameters will be based on plasma concentration of DFF332 single agent and in combination.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2021
- Study start30 Nov 2021
- Primary completion13 Feb 2026
- Study completion13 Feb 2026
Why it stopped: Business decision and not related to safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Renal CellStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04895748
- Sponsor's protocol ID
- CDFF332A12101
- Other IDs
- 2024-513379-41
- Status last verified
- Mar 2026
- First submitted
- 19 May 2021
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/Ib, Open-label, Multi-center Study of DFF332 as a Single Agent and in Combination With Everolimus or IO Agents in Patients With Advanced/Relapsed ccRCC and Other Malignancies With HIF2α Stabilizing Mutations
- ClinicalTrials.gov ID
- NCT04895748
- Acronym / sponsor ID
- CDFF332A12101
- Conditions
- Carcinoma, Renal Cell
- Keywords
- ccRCC, RCC, Kidney, DFF332, NIR178, PDR001, RAD001, Everolimus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision and not related to safety concerns
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 13 Feb 2026 (actual)
- Study completion
- 13 Feb 2026 (actual)
- First posted
- 20 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a first in human study of DFF332, a small molecule that targets a protein called HIF2α. By acting on HIF2α, DFF332 may be able to stop the growth of certain types of cancer. DFF332 was planned to be tested at different doses as single agent and in combination with Everolimus (RAD001, an mTOR inhibitor), and also in combination with Spartalizumab (PDR001, an anti-PD1) plus Taminadenant (NIR178, an adenosine A2A receptor antagonist), in patients with advanced clear cell renal cell carcinoma and other malignancies with HIF stabilizing mutations.
Detailed description
This was a first in human (FIH), Phase I/Ib, open-label, multi-center study of DFF332 as a single agent and in combination with Everolimus or Spartalizumab plus Taminadenant in patients with advanced clear cell renal cell carcinoma and other malignancies with HIF stabilizing mutations.
The study consisted of two parts, dose escalation and dose expansion. The dose escalation part of the study initially evaluated DFF332 single agent. Dose escalation groups receiving DFF332 in combination with Everolimus or DFF332 in combination with Spartalizumab plus Taminadenant were planned to be opened after at least two dose levels of single agent DFF332 had been evaluated.
The dose expansion part of single agent included two treatment arms: Arm1A was planned to enroll ccRCC patients (age 18 yo or above) and Arm1B was planned to enroll patients with malignancies harboring HIF stabilizing mutations (age 12 yo and above). These included the following:
- Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)
- Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)
- Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome)
- Malignancies with EPAS1/HIF2A mutations
- Malignancies with ELOC/TCEB1 mutations
The expansion part of the combination therapies was planned to enroll patients with ccRCC and to include Arm2A (DFF332 with Everolimus) and Arm3A (DFF332 with Spartalizumab plus Taminadenant).
Novartis halted enrollment of study CDFF332A12101 in September 2023 due to business reasons and not due to safety concerns. The DFF332 single agent dose expansion arms and the dose escalation and expansion of the combination arms did not open.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Dose Escalation DFF332 | Experimental | Drug: DFF332DFF332 Single Agent |
| Arm 2 Dose Escalation DFF332 + Everolimus | Experimental | Drug: DFF332, Drug: RAD001Combination treatment DFF332 + Everolimus. This arm did not open. |
| Arm 3 Dose Escalation DFF332 + Spartalizumab + Taminadenant | Experimental | Drug: DFF332, Drug: PDR001, Drug: NIR178Combination treatment DFF332 + Spartalizumab + Taminadenant. This arm did not open. |
| Arm 1a Dose Expansion DFF332 in ccRCC | Experimental | Drug: DFF332DFF332 Single Agent in patients with ccRCC (age 18 years old and above). This arm did not open. |
| Arm 1b Dose Expansion DFF332 in HIF stabilizing malignancies | Experimental | Drug: DFF332DFF332 Single Agent in patients with HIF stabilizing malignancies (age 12 years old and above). This arm did not open. |
| Arm 2a Dose Expansion DFF332 + Everolimus in ccRCC | Experimental | Drug: DFF332, Drug: RAD001Combination treatment DFF332 + Everolimus in patients with ccRCC (age 18 years old and above). This arm did not open. |
| Arm 3a Dose Expansion DFF332 + Spartalizumab + Taminadenant in ccRCC | Experimental | Drug: DFF332, Drug: PDR001, Drug: NIR178Combination treatment DFF332 + Spartalizumab + Taminadenant in patients with ccRCC (age 18 years old and above). This arm did not open. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and female ≥ 18 years of age For Arm 1B: Male and female of age ≥ 12 years of age
- Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC). Disease must be measurable as determined by RECIST v1.1.
- For Arm 1B: histologically confirmed and documented malignancies in the context of the following cancer predisposing syndromes/disorders or harboring somatic mutations on one of these genes:
- Patient with unresectable, locally advanced or metastatic ccRCC with documented disease progression following all standard of care therapy, including PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy as monotherapy or in combination.
- Escalation: No restriction on the number of prior treatments Expansion (with the exception of Arm 1B): Up to 3 prior lines of treatment for advanced/metastatic disease For Arm 1B: Patients must have either metastatic disease or locally advanced disease that is unresectable or that patients be unfit for resection or other treatment modalities. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, and have no available therapies of proven clinical benefit; or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
Key exclusion criteria (18 listed)
- History of seizure disorder \& extrapyramidal (EPS) symptoms
- Impaired cardiac function or clinically significant cardiac disease, including any of the following:
- Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
- Patient previously treated with a HIF2α inhibitor.
- Uncontrolled concurrent illness including, but not limited to, ongoing active infection, uncontrolled hypertension, active peptic ulcer disease or gastritis, active bleeding diatheses, including any Patient known to have evidence of acute or chronic hepatitis B, hepatitis C, human immunodeficency virus (HIV), or a psychiatric illness/social situation that in the investigator's opinion would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion parts but not in the escalation parts.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DFF332Hif2alpha inhibitor | Drug | Arm 1 Dose Escalation DFF332, Arm 1a Dose Expansion DFF332 in ccRCC, Arm 1b Dose Expansion DFF332 in HIF stabilizing malignancies, Arm 2 Dose Escalation DFF332 + Everolimus, Arm 2a Dose Expansion DFF332 + Everolimus in ccRCC, Arm 3 Dose Escalation DFF332 + Spartalizumab + Taminadenant, Arm 3a Dose Expansion DFF332 + Spartalizumab + Taminadenant in ccRCC |
| RAD001Also: EverolimusmTOR inhibitor | Drug | Arm 2 Dose Escalation DFF332 + Everolimus, Arm 2a Dose Expansion DFF332 + Everolimus in ccRCC |
| PDR001Also: Spartalizumabanti-PD-1 | Drug | Arm 3 Dose Escalation DFF332 + Spartalizumab + Taminadenant, Arm 3a Dose Expansion DFF332 + Spartalizumab + Taminadenant in ccRCC |
| NIR178Also: TaminadenantAdenosine A2A antagonist receptor | Drug | Arm 3 Dose Escalation DFF332 + Spartalizumab + Taminadenant, Arm 3a Dose Expansion DFF332 + Spartalizumab + Taminadenant in ccRCC |
Primary outcome
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: 3 years
Number of participants with AEs/SAEs to characterize the safety and tolerability of DFF332 as a single agent, in combination with Everolimus (RAD001), and in combination with Spartalizumab (PDR001) plus Taminadenant (NIR178) in patients with advanced clear cell Renal Cell Carcinoma (ccRCC) and advanced malignancies with Hypoxia Inducible Factor (HIF) stabilizing mutations
Number of participants with dose interruptions and dose reductions
Time frame: 3 years
Number of participants with dose interruptions and dose reductions to characterize the tolerability of DFF332 as a single agent, in combination with Everolimus (RAD001), and in combination with Spartalizumab (PDR001) plus Taminadenant (NIR178) in patients with advanced ccRCC and advanced malignancies with HIF stabilizing mutations.
Dose intensity for DFF332 for dose escalation and expansion
Time frame: 3 years
Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 days) for DFF332 as a single agent and in combinations
Time frame: 28 days
Number of participants with DLTs
7 secondary outcomes
Overall Response Rate (ORR)
Time frame: 3 years
Best Overall Response (BOR)
Time frame: 3 years
Progression Free Survival (PFS) for Recommended Dose (RD) only
Time frame: 3 years
Duration of Response (DOR) for Recommended Dose (RD) Only
Time frame: 3 years
Disease Control Rate (DCR)
Time frame: 3 years
Maximum Concentration (Cmax) of DFF332 single agent and combination
Time frame: 3 years
Area under the concentration-time curve (AUC) of DFF332 single agent and combination
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Business decision and not related to safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DFF332, RAD001 and PDR001 in people with Carcinoma, Renal Cell, run by Novartis Pharmaceuticals at 11 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Czechia, France, Italy, Japan and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business decision and not related to safety concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.