TNO155 +/- Nazartinib for Advanced Cancers

No longer recruiting at 24 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: KRAS, Cardiac disease, 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 tests a new treatment called TNO155, both alone and with another drug, nazartinib, to determine their safety and tolerability for people with advanced solid tumors. Researchers focus on patients whose cancer has not responded to standard treatments or for whom no effective standard therapy exists. The trial consists of two parts: one tests TNO155 alone, and the other tests it with nazartinib, specifically for people with a type of lung cancer that has certain mutations. Those who have tried standard treatments without success and have no specific genetic tumor mutations may be suitable for this trial.

As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using immunosuppressive agents or chronic corticosteroids.

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

Research has shown that TNO155 is generally well-tolerated by patients with advanced solid tumors. Early results indicate that TNO155 is safe and effective at certain doses, targeting the problem without causing excessive side effects.

Regarding the combination of TNO155 with nazartinib, safety information is still being gathered. Nazartinib has demonstrated an acceptable safety level in other studies, suggesting that the combination might also be safe, though further research is needed to confirm this.

In summary, both treatments are still under study to fully understand their safety, but early data suggests they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TNO155 and its combination with nazartinib because these treatments offer a fresh approach to tackling advanced cancers, especially EGFR mutant non-small cell lung cancer (NSCLC). TNO155 works by targeting the SHP2 protein, which plays a key role in cancer cell signaling, making it different from the usual EGFR inhibitors like erlotinib or gefitinib. When paired with nazartinib, an EGFR inhibitor, it may offer a one-two punch against cancer cells by simultaneously blocking key pathways that tumors use to grow and survive. This innovative mechanism of action could potentially overcome resistance seen with current treatments, providing new hope for patients.

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

Research has shown that TNO155, one of the treatments in this trial, holds promise for treating advanced cancers by blocking SHP2, a protein that aids tumor growth. This blocking action may help overcome resistance to other cancer drugs and enhance their effectiveness. Studies have demonstrated that TNO155 can target specific cancer mutations, offering hope for patients with resistant tumors.

Another treatment arm in this trial uses TNO155 in combination with nazartinib. Nazartinib targets certain mutations in non-small-cell lung cancer. Together, these drugs could block signals that promote cancer, making them a strong treatment option for advanced cancers. ^{3 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors like melanoma or lung cancer, who've tried standard treatments without success or can't tolerate them. They must understand the study and follow its schedule, agree to effective contraception, and have an acceptable level of physical function (ECOG ≤2). People with certain viral infections, specific genetic mutations in their tumors, significant health issues including heart disease, eye conditions that increase injury risk, active severe skin disorders or bowel inflammation are excluded.

Inclusion Criteria

I have been tested for Hepatitis B and C.

I can perform daily activities with minimal assistance.

My condition worsened after standard treatment, or standard treatments aren't suitable for me.

Exclusion Criteria

You have a history of being HIV positive.

Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive TNO155 alone or in combination with EGF816 (nazartinib) to determine the maximum tolerated dose

21-28 days per cycle

At least once per treatment cycle

Dose Expansion

Participants receive the recommended dose of TNO155 alone or in combination with EGF816 (nazartinib) to further evaluate safety and efficacy

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

What Are the Treatments Tested in This Trial?

Interventions

• TNO155
• TNO155 in combination with EGF816 (nazartinib)

Trial Overview The trial is testing TNO155 alone and combined with EGF816 (nazartinib) to find safe doses for future studies. It's a first-in-human study focusing on safety and tolerability in patients with selected types of advanced solid tumors. The goal is also to determine the recommended dose levels for subsequent research phases.

How Is the Trial Designed?

Group I: TNO155 in combination with EGF816 (nazartinib) Experimental Treatment 1 Intervention

TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC

Group II: TNO155 Experimental Treatment 1 Intervention

TNO155 for oral administration

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

Gefitinib, an EGFR inhibitor, was effective in shrinking tumors in two patients with advanced non-small cell lung carcinoma (NSCLC) before they underwent surgery, demonstrating its potential as a preoperative treatment.

Both patients experienced significant tumor reduction and underwent potentially curative surgeries, but they relapsed after stopping adjuvant gefitinib therapy, indicating the need for further research on long-term outcomes and survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Down-staging of EGFR mutation-positive advanced lung carcinoma with gefitinib followed by surgical intervention: follow-up of two cases. Levchenko, EV., Moiseyenko, VM., Matsko, DE., et al.[2018]

The ARTEMIS study shows that combining the VEGF inhibitor bevacizumab with the EGFR inhibitor erlotinib significantly improves progression-free survival in patients with EGFR mutant non-small-cell lung cancer by over 6 months.

Patients with brain metastases and the EGFR L858R mutation experienced even greater benefits, highlighting the importance of personalized treatment strategies in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ARTEMIS highlights VEGF inhibitors as effective partners for EGFR TKIs in EGFR mutant NSCLC. Le, X., Nilsson, MB., Robichaux, JP., et al.[2021]

In a study involving 73 patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC), the combination of tepotinib and gefitinib showed promising efficacy, particularly in patients with high MET overexpression or MET amplification, leading to longer progression-free survival (PFS) compared to standard chemotherapy.

The treatment was generally well-tolerated, with no dose-limiting toxicities observed, although some patients experienced grade 3 or worse adverse events, such as increased amylase and lipase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Wu, YL., Cheng, Y., Zhou, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03114319

Study Details | TNO155 Dose Finding Study for Solid Tumors This study has been designed as a Phase I, open-label, dose finding study with a dose escalation part and a dose expansion part in adult patients with selected ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.3005

TNO155 SHP2 inhibitor dose finding study in solid tumors TNO155 shows favorable pharmacokinetic properties and promising early safety and tolerability data at doses with evidence of target inhibition.

3. aacrjournals.org aacrjournals.org/clincancerres/article/27/1/342/83701/Combinations-with-Allosteric-SHP2-Inhibitor-TNO155

Combinations with Allosteric SHP2 Inhibitor TNO155 to Block ... These data suggest that TNO155 can overcome acquired resistance to EGFR TKIs and also enhance their efficacy, providing a strong rationale to explore this ...

4. onclive.com onclive.com/view/tno155-jdq433-combo-elicits-responses-is-tolerable-in-kras-g12c-solid-tumors

TNO155/JDQ433 Combo Elicits Responses, Is Tolerable in ... The combination of the SHP2 inhibitor TNO155 and the KRAS G12C inhibitor JDQ433 showed antitumor activity in patients with KRAS G12C-mutated solid tumors.

5. withpower.com withpower.com/trial/phase-1-melanoma-4-2017-0ec07

TNO155 +/- Nazartinib for Advanced Cancers Nazartinib, a component of the treatment, has shown effectiveness in targeting specific mutations in non-small-cell lung cancer, particularly those resistant to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03114319

Dose Finding Study of TNO155 in Adult Patients With ... The purpose of this first in human (FIH) trial was to characterize the safety and tolerability of the SHP2 inhibitor TNO155 alone and in combination with EGF816 ...

7. onclive.com onclive.com/view/tno155-plus-spartalizumab-or-ribociclib-elicits-disease-control-is-safe-in-advanced-solid-tumors

TNO155 Plus Spartalizumab or Ribociclib Elicits Disease ... TNO155 plus spartalizumab or ribociclib was well tolerated and demonstrated disease control in patients with advanced solid tumors.

8. cancernetwork.com cancernetwork.com/view/shp2-inhibition-with-tno155-for-advanced-solid-tumors-shows-initial-safety-favorable-pharmacokinetic-data

SHP2 Inhibition With TNO155 for Advanced Solid Tumors ... Reliable SHP2 inhibition and an encouraging safety and tolerability profile were noted with use of TNO155 in adults with advanced solid ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10863183/

Oncogenic alterations in advanced NSCLC: a molecular super ... Recently the efficacy and safety data from 48 patients with treatment-naive, advanced HER2-mutant NSCLC treated with the pan-HER receptor ...