KAZ954 Combinations for Cancer

No longer recruiting at 22 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Corticosteroids

Disqualifiers: CNS metastases, Cardiac impairment, HIV, 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 explores the safety and optimal dosage of a new treatment, KAZ954, used alone and with other drugs (PDR001, NIR178, and NZV930), for individuals with advanced solid tumors. The aim is to determine how well patients with metastatic, non-surgical cancer can tolerate these treatments. This trial suits those with metastatic cancer who are willing to undergo tumor biopsies. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

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 has shown that KAZ954, whether used alone or with other treatments, is generally safe and well tolerated. One study found no safety concerns with KAZ954, making future trials promising for people with advanced cancer. KAZ954 was safe at all tested doses, ranging from 150 mg to 1200 mg every two weeks.

For the combination treatments:

1. **KAZ954 + PDR001**: No safety concerns were found that would halt further studies. Preliminary data suggest it has a good safety profile.

2. **KAZ954 + NIR178**: This combination was also safe, with researchers reporting no significant safety issues.

3. **KAZ954 + NZV930**: Similarly, this combination raised no safety concerns, and previous studies did not highlight any major problems.

These findings suggest that the treatments are safe for further testing in humans, but this remains an early phase trial. Researchers are primarily focused on understanding the safety and correct dosage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced solid tumors because they introduce new mechanisms of action that differ from traditional therapies like chemotherapy and radiation. KAZ954 is unique as it targets specific pathways involved in tumor growth, potentially reducing cancer cell proliferation more precisely. When combined with PDR001, NZV930, or NIR178, KAZ954 may enhance the immune system's ability to attack cancer cells, offering a novel approach compared to conventional treatments. This combination strategy aims to improve efficacy and minimize side effects, providing hope for better outcomes in patients with advanced cancers.

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

Research has shown that KAZ954, one of the treatments in this trial, may help treat advanced solid tumors. Studies have found it to be safe and well-tolerated, and it works by blocking a target called ENTPD2, which might help stop cancer cells from growing. In this trial, some participants will receive KAZ954 with PDR001, which can boost the immune system's ability to fight cancer by blocking certain pathways. Another group will receive the combination of KAZ954 with NZV930, aiming to improve treatment by targeting similar pathways, even though past data on NZV930 alone showed limited benefits. Additionally, early data suggest that using KAZ954 with NIR178, as tested in another arm of this trial, to block different cancer pathways simultaneously could enhance the treatment's effects. Overall, these combinations aim to better use the body's own defenses against cancer. ^{3 4 5 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Inclusion Criteria

ECOG Performance Status of <2.

You have advanced cancer that cannot be treated with surgery to cure it.

Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening and during the study.

Exclusion Criteria

You have experienced a severe allergic reaction to any ingredient in the study drug or similar medications.

There may be additional requirements or restrictions for participating in the study that are not listed here.

You have heart problems, HIV, a history of tuberculosis, or have been taking steroids for a long time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

The dose escalation part estimated the MTD and/or RD and tested different dosing schedules.

Up to 52 weeks

Dose Expansion

Planned to use the MTD/RDE determined in the dose escalation part to assess the activity, safety, and tolerability of the investigational products.

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KAZ954
• NIR178
• NZV930
• PDR001

How Is the Trial Designed?

Group I: Arm D Experimental Treatment 2 Interventions

KAZ954 + NZV930

Group II: Arm C Experimental Treatment 2 Interventions

KAZ954 + NIR178

Group III: Arm B Experimental Treatment 2 Interventions

KAZ954 + PDR001

Group IV: Arm A Experimental Treatment 1 Intervention

KAZ954

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

Citations

1. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/B114/730800/Abstract-B114-A-Phase-1-1b-study-of-KAZ954-alone

Abstract B114: A Phase 1/1b study of KAZ954 alone and in ... KAZ was considered to be safe and well tolerated at all doses, and PK/PD analysis suggest effective ENTPD2 inhibition from a dose range of 150 to 1200 mg Q2W.

2. synapse.patsnap.com synapse.patsnap.com/drug/996e8045b64842df8897416dd6b5d8f6

KAZ-954 - Drug Targets, Indications, Patents The trial of NZV930 was “terminated early because data review showed low likelihood of efficacy in the patients recruited in that clinical ...

3. withpower.com withpower.com/trial/early-phase-1-neoplasms-1-2020-a968b

KAZ954 Alone and With PDR001, NZV930 and NIR178 in ... This trial is testing a new drug called KAZ954 alone and with other drugs to find the safest and most effective dose for patients with advanced cancer.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223009757

Drugs targeting adenosine signaling pathways: A current ... The FDA approved ticagrelor tablets in 2011 to reduce the rate of MI and cardiovascular death in adult patients with acute coronary syndrome (Table 1). The ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8830302/

Next steps for clinical translation of adenosine pathway ... Preliminary data have demonstrated an optimal safety profile and enhanced overall response rates in several early phase clinical trials with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04237649

NCT04237649 | KAZ954 Alone and With PDR001, NZV930 ... The primary objective of the trial was to characterize the safety, tolerability, and maximum tolerated dose (MTD)/recommended dose (RD) for expansion of single ...

7. novctrd.com novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2305

Thank you! The researchers concluded there were no safety concerns that would prevent future trials of KAZ954 alone or with PDR001 or NIR178 in people with advanced cancer ...