Sapanisertib + Telaglenastat for Lung Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Proton pump inhibitors

Disqualifiers: Chemotherapy, Radiotherapy, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 27 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of two drugs, sapanisertib and telaglenastat, to determine their effectiveness in treating advanced non-small cell lung cancer that has spread. The goal is to identify the optimal dose and understand any side effects when these drugs are used together. They work by blocking certain enzymes that promote cancer cell growth. This trial may suit individuals with stage IV lung cancer who have not responded to treatments like platinum-based chemotherapy or immune therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you should be cautious if you are taking medications that interact with CYP2C9, as CB-839 HCl may affect them. It's important to discuss your current medications with the trial team.

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

Research shows that the combination of sapanisertib and telaglenastat (also known as CB-839 HCl) is under evaluation for safety in people with advanced non-small cell lung cancer. Previous studies have assessed how well patients tolerate these drugs together, aiming to determine the right dose and understand any side effects.

In earlier research, some patients experienced mild to moderate side effects such as tiredness, nausea, and changes in appetite, while more serious side effects were less common. The studies aim to find a dose that is both effective and safe.

As a phase 1 trial, this is an early step in testing. This phase evaluates the treatment's safety and potential side effects. While some side effects have been noted, ongoing research seeks to manage these and ensure the treatment's safety for future use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sapanisertib and Telaglenastat for lung cancer because these treatments target cancer cells in a unique way. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Sapanisertib specifically inhibits a pathway involved in cell growth and survival, potentially leading to fewer side effects. Telaglenastat, on the other hand, blocks glutaminase, an enzyme critical for cancer cell metabolism, effectively starving the cancer cells. By combining these two mechanisms, the treatment aims to more precisely target cancer cells while sparing healthy tissue, offering hope for improved effectiveness and reduced toxicity compared to current standard treatments.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

Research shows that combining two drugs, sapanisertib and telaglenastat, may help treat advanced non-small cell lung cancer (NSCLC). In this trial, participants will receive both drugs. They might work by blocking certain enzymes that cancer cells need to grow, potentially stopping tumor growth. Early results suggest that patients with specific types of lung cancer might benefit from this treatment. Some studies have found that it may slow the disease's progression. While more research is needed, these early findings offer hope for people with advanced NSCLC. ^{1 2 3 4 5}

Who Is on the Research Team?

Jonathan W. Riess

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that worsened after platinum-based chemotherapy or PD-(L)1 inhibitors. Participants must have specific mutations if they've had targeted therapies, manageable brain metastases, and meet certain health criteria like stable blood sugar and organ function. Pregnant women, those unable to swallow pills, or with severe illnesses are excluded.

Inclusion Criteria

ECOG-ACRIN performance status 0-2

Patients must have stage IV or recurrent/metastatic NSCLC and have progressed on or after platinum-based chemotherapy and/or PD-(L)1 immune checkpoint inhibitor

Dose escalation: patients with NSCLC known to harbor EGFR, ALK, ROS1, BRAF V600E/K activating mutations must have also progressed on appropriate FDA-approved targeted therapies

Exclusion Criteria

HIV-infected patients

You are currently taking part in another study with a new or experimental treatment.

Patients who have had chemotherapy within 3 weeks or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glutaminase inhibitor CB-839 hydrochloride orally twice daily and sapanisertib once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 27 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up occurring quarterly.

Quarterly follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Sapanisertib
• Telaglenastat Hydrochloride

Trial Overview The trial tests the safety and optimal doses of two anti-cancer drugs: CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib), when used together in patients with NSCLC. These drugs aim to block enzymes essential for tumor cell growth.

How Is the Trial Designed?

Group I: Treatment (CB-839 HCl, sapanisertib) Experimental Treatment 2 Interventions

Patients receive glutaminase inhibitor CB-839 hydrochloride PO BID and sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of sapanisertib, serabelisib, and paclitaxel was found to be safe and well tolerated in a Phase I trial involving 19 patients with advanced solid tumors, with manageable adverse effects such as decreased white blood cells and anemia.

Preliminary efficacy results were promising, showing an overall response rate of 47% and a clinical benefit rate of 73%, particularly in patients with specific genetic abnormalities, indicating potential effectiveness in a challenging treatment population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of dual PI3K/mTOR inhibition by Sapanisertib and Serabelisib in combination with paclitaxel in patients with advanced solid tumors. Starks, DC., Rojas-Espaillat, L., Meissner, T., et al.[2022]

In a phase II trial involving 42 patients with advanced non-small cell lung cancer (NSCLC), talabostat mesilate was found to be well tolerated, with some patients showing partial or complete responses.

However, the study concluded that talabostat did not enhance the effectiveness of docetaxel, a standard chemotherapy drug, in treating NSCLC after previous treatments failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer. Eager, RM., Cunningham, CC., Senzer, N., et al.[2018]

In a phase I study involving 61 patients with advanced solid tumors, the investigational drug sapanisertib (TAK-228) was found to be well tolerated, with maximum tolerated doses established for different administration schedules, and no significant differences in adverse events across treatment regimens.

TAK-228 demonstrated antitumor activity, particularly when combined with paclitaxel, showing objective response rates of 18% for the combination therapy and 12% for the daily administration, indicating its potential effectiveness in treating certain malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the investigational oral mTORC1/2 inhibitor sapanisertib (TAK-228): tolerability and food effects of a milled formulation in patients with advanced solid tumours. Moore, KN., Bauer, TM., Falchook, GS., et al.[2022]

The combination of sapanisertib, a mTORC1/2 inhibitor, with carboplatin and paclitaxel showed a manageable safety profile in patients with tumors that have mTOR pathway alterations, with no unexpected toxicities reported.

Among 17 evaluable patients, there were signs of preliminary antitumor activity, with 2 achieving partial responses and a median progression-free survival of 3.84 months, indicating potential efficacy in advanced malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies. Alhalabi, O., Groisberg, R., Zinner, R., et al.[2023]

In a phase 2 trial involving 21 patients with previously treated small-cell lung cancer (SCLC), panobinostat (LBH589) demonstrated a favorable safety profile, with most side effects being mild gastrointestinal issues and low-grade thrombocytopenia.

Despite the trial being prematurely closed due to a lack of overall activity, two patients experienced significant tumor shrinkage, and three others had stable disease for several weeks, suggesting that LBH589 may have potential as a treatment option worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in pretreated patients with small-cell lung cancer. de Marinis, F., Atmaca, A., Tiseo, M., et al.[2018]

Sapanisertib, an oral mTORC1/mTORC2 inhibitor, showed a manageable safety profile in a Phase 1 study involving 31 patients with advanced solid tumors, with maximum tolerated doses identified for different dosing schedules.

Preliminary results indicated antitumor activity, with one complete response and nine partial responses observed, particularly in patients with renal cell carcinoma and endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Voss, MH., Gordon, MS., Mita, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7834952/

A Phase 1 Trial of MLN0128 (sapanisertib) and CB-839 ... This phase 1 study will determine the RED and preliminary efficacy of sapanisertib (MLN0128) and CB-839 in advanced NSCLC with a focus on subsets of LSCC and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04250545

NCT04250545 | Testing of the Anti Cancer Drugs CB-839 ... To examine preliminary efficacy of CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in squamous cell lung cancers (LSCC) and in select, molecularly-defined ...

3. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(20)30308-9/fulltext

Phase 1 Trial of MLN0128 (Sapanisertib) and CB-839 HCl ... This phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non–small-cell lung ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04250545?term=CB-839&viewType=Table&rank=8

Study Details | Testing of the Anti Cancer Drugs CB-839 ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730420303089

Phase 1 Trial of MLN0128 (Sapanisertib) and CB-839 HCl ... This phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non–small-cell lung cancer.