DKY709 + PDR001 for Cancer

Recruiting at 14 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

98 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drugs DKY709 and PDR001 for cancer treatment?

The research on immune checkpoint inhibitors, like PDR001, shows that they can be effective in treating certain types of cancer, such as colorectal cancer with specific genetic features, by helping the immune system attack cancer cells. Additionally, studies on similar drugs targeting the same pathways suggest potential benefits in cancer treatment. ^{1 2 3 4 5}

What safety data exists for DKY709 + PDR001 in cancer treatment?

PD-1/PD-L1 inhibitors, like PDR001, have shown manageable safety profiles in cancer treatment, making them suitable for outpatient use. They have been used in combination with other therapies and have demonstrated less and controllable toxicity and side effects. ^{6 7 8 9 10}

What makes the DKY709 + PDR001 drug unique for cancer treatment?

The DKY709 + PDR001 drug combination is unique because it targets the PD-1/PD-L1 pathway, which is involved in immune suppression by cancer cells. This approach can potentially enhance the immune system's ability to fight cancer, offering a novel strategy compared to traditional treatments that do not focus on immune checkpoint blockade. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial tests DKY709 alone and with PDR001 in patients with certain cancers who didn't respond to previous treatments. It aims to see if these drugs can improve the immune system's ability to fight cancer.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. England 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. [2022]

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

Clinical Development of Immunotherapy for Deficient Mismatch Repair Colorectal Cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer. [2022]

4. United States 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. [2023]

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

CD73: A potential biomarker for anti-PD-1 therapy. [2021]

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

Targeting the DNA Damage Response in Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Research progress of tumor targeted drug delivery based on PD-1/PD-L1. [2022]

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

Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity. [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Mutations Defining Patient Cohorts With Elevated PD-L1 Expression in Gastric Cancer. [2020]

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

PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways. [2019]

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

The clinical significance of PD-L1 in advanced gastric cancer is dependent on ARID1A mutations and ATM expression. [2021]

15. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants. [2021]