DKY709 + PDR001 for Cancer

Not currently recruiting at 15 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Disqualifiers: CNS metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for certain advanced cancers, such as non-small cell lung cancer (NSCLC), melanoma, and nasopharyngeal cancer (NPC). It evaluates the safety and tolerability of a new drug, DKY709, both alone and in combination with PDR001, an immunotherapy. Researchers aim to determine the effectiveness of these treatments against tumors, particularly in patients who have not responded to other therapies. Suitable candidates have advanced cancer that has not responded to standard treatments and are willing to undergo tumor biopsies (small samples of the tumor taken for study). As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that DKY709 and PDR001 are currently being tested for safety, both separately and together. These tests aim to assess how well people tolerate the treatment. Since the trial is in its early stages, researchers are still gathering information about safety.

In previous studies, DKY709 has shown potential as a treatment, but researchers are still learning about all its effects. Similarly, when PDR001 is used with DKY709, researchers monitor for any side effects. Because these treatments are in early testing, not all safety aspects are known. However, this phase focuses on safety, and the treatments are usually given in low doses to observe reactions.

If the treatments were unsafe, they wouldn't progress beyond these initial stages. Since they are in early trials, participants can expect close monitoring for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DKY709 + PDR001 for cancer because it combines two innovative therapies that work together to boost the immune system's ability to fight cancer. DKY709 is a small molecule that targets a specific protein, potentially making cancer cells more vulnerable to immune attack, while PDR001 is an antibody that inhibits PD-1, a protein that cancer cells use to evade immune detection. This combination aims to enhance the immune response against tumors more effectively than current treatments, which often focus on just one pathway.

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

Research has shown that DKY709, one of the treatments in this trial, may reduce tumor growth both alone and when combined with PDR001. DKY709 breaks down a protein called IKZF2, which plays a role in the immune system's fight against cancer. In animal studies, DKY709 slowed tumor growth and strengthened the immune response. When combined with PDR001, another treatment in this trial that aids the immune system in attacking cancer, the combination may prove even more effective. Early results from patients with advanced solid tumors suggest similar benefits in humans, offering hope for those with certain cancers. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults (≥18 years) with advanced cancers like NSCLC, melanoma, NPC, mssCRC, or TNBC who have progressed after standard therapy or are intolerant to it. Participants must have measurable disease and be willing to undergo tumor biopsies. Excluded are those with significant heart issues, severe allergies to study drugs' ingredients, certain abnormal lab values, symptomatic CNS metastases or recent cardiac events.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

For the additional part of the study, patients must have one of the following: non-small cell lung cancer with a history of PD-L1 levels of at least 1% and disease progression after at least 4 months of stable or improved condition with previous anti-PD-L1 treatment; previously treated cutaneous melanoma with documented disease progression after anti-PD-1/PD-L1 therapy; nasopharyngeal carcinoma (NPC) without prior anti-PD-1/PD-L1 therapy; microsatellite stable colorectal cancer (mssCRC) without prior anti-PD-1/PD-L1 therapy; triple-negative breast cancer (TNBC) without prior anti-PD-1/PD-L1 therapy.

My advanced cancer has worsened after standard treatment, or I can't tolerate it, and no other standard treatments work for me.

Exclusion Criteria

I do not have serious heart problems or recent heart attacks.

Your kidney function, liver function, and blood cell counts need to be within certain ranges to qualify for the study.

I have brain metastases that are stable, and I haven't taken steroids for 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Characterize the safety and tolerability of DKY709 and DKY709 in combination with PDR001

1 month

Dose Expansion

Further assess safety, tolerability, PK/PD, and anti-tumor activity at the MTD/RD

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DKY709
• PDR001

Trial Overview The trial is testing the safety and effectiveness of DKY709 alone and in combination with PDR001 for treating various advanced solid tumors. It's a phase I/Ib study that includes an initial dose escalation to find the maximum tolerated dose followed by expansion at this dose to further evaluate the treatments.

How Is the Trial Designed?

Group I: DKY709 + PDR001 Experimental Treatment 2 Interventions

Combination therapy with DKY709 and PDR001

Group II: DKY709 Experimental Treatment 1 Intervention

DKY709 monotherapy

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

In a phase IB trial involving 50 patients with advanced solid tumors, the combination of LY2780301 and gemcitabine demonstrated manageable toxicity, with the maximum tolerated dose established at 500 mg of LY2780301 and 750 mg/m2 of gemcitabine.

The treatment showed promising antitumor activity, with a disease control rate of 74% at cycle 2 and partial responses in 5% of patients, particularly in those with alterations in the PI3K/AKT/mTOR signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and antitumour activity of LY2780301 (p70S6K/AKT inhibitor) in combination with gemcitabine in molecularly selected patients with advanced or metastatic cancer: a phase IB dose escalation study. Angevin, E., Cassier, PA., Italiano, A., et al.[2022]

M2698, an oral dual inhibitor targeting the p70S6K/AKT pathway, was well tolerated in 101 patients with advanced cancer, showing manageable side effects primarily related to gastrointestinal issues and fatigue.

In patients with advanced breast cancer resistant to standard therapies, M2698 demonstrated some antitumor activity, with two patients achieving partial responses when combined with trastuzumab or tamoxifen, indicating potential effectiveness in overcoming treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer. Tsimberidou, AM., Shaw, JV., Juric, D., et al.[2022]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

Citations

1. cell.com cell.com/cell-chemical-biology/fulltext/S2451-9456(23)00054-5

Discovery and characterization of a selective IKZF2 glue ... In vivo, treatment with NVP-DKY709 delayed tumor growth in mice with a humanized immune system and enhanced immunization responses in cynomolgus ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12046021/

Development of PVTX-405 as a potent and highly selective ... Oral administration of DKY709 induced potent and effective IKZF2 degradation. Two selective IKZF2 degraders, DKY709 and PLX-4545 (Fig. 1a) have entered Phase 1 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03891953

NCT03891953 | Study of Safety and Efficacy of DKY709 ... This is a phase I/Ib, open label study. The escalation portion will characterize the safety and tolerability of DKY709 and DKY709 in combination with PDR001 ...

4. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/4512/740593/Abstract-4512-Discovery-of-highly-potent-selective

Abstract 4512: Discovery of highly potent, selective, and orally ... Leveraging an Immunomodulatory drug (IMiD), Novartis has developed the IKZF2 degrader DKY709, which is currently undergoing Phase I clinical ...

5. novartis.com novartis.com/news/media-releases/novartis-announces-early-clinical-data-unique-krasg12c-inhibitor-american-association-cancer-research-annual-meeting

Novartis announces early clinical data for unique ... Clinical data were drawn from a study (NCT03891953) of advanced solid tumors in which DKY709 is being investigated as a monotherapy and in ...

6. pharmacytimes.com pharmacytimes.com/view/novartis-releases-positive-phase-1b-2-clinical-data-for-jdq443-for-treatment-of-nsclc

Novartis Releases Positive Phase 1b/2 Clinical Data for ... The clinical data were drawn from a study that investigated DKY709 as a monotherapy and in combination with the anti-PD-1 antibody ...