Sapanisertib + Telaglenastat for Lung Cancer

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

85 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/Ib trial studies the side effects and best dose of CB-839 HCl when given together with sapanisertib in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). CB-839 HCl and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

What data supports the effectiveness of the drug Sapanisertib + Telaglenastat for lung cancer?

Research shows that Sapanisertib, when used with other cancer drugs like paclitaxel, has shown promise in treating various advanced solid tumors by restoring sensitivity to treatments and enhancing cancer cell killing. Although specific data for lung cancer is not provided, its effectiveness in other cancers suggests potential benefits. ^{1 2 3 4 5}

Is the combination of Sapanisertib and Telaglenastat safe for humans?

Sapanisertib has been studied in various trials and generally shows a manageable safety profile, though some patients experienced side effects like anemia (low red blood cell count), neutropenia (low white blood cell count), and thrombocytopenia (low platelet count). There were no unexpected toxicities reported in these studies. ^{1 2 3 4 5}

What makes the drug combination of Sapanisertib and Telaglenastat unique for lung cancer treatment?

The combination of Sapanisertib and Telaglenastat is unique because it targets specific pathways involved in cancer cell growth and survival, potentially offering a novel approach compared to traditional chemotherapy drugs. Sapanisertib inhibits a protein called mTOR, which is involved in cell growth, while Telaglenastat targets cancer cell metabolism, making this combination a promising new strategy for treating lung cancer. ^{6 7 8 9 10}

Research Team

Jonathan W. Riess

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies. [2023]

3. United States 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. [2022]

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

Biomarker-Based Phase II Study of Sapanisertib (TAK-228): An mTORC1/2 Inhibitor in Patients With Refractory Metastatic Renal Cell Carcinoma. [2023]

5. England 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. [2022]

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

A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in pretreated patients with small-cell lung cancer. [2018]

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

New chemotherapeutic agents in the treatment of non-small cell lung cancer: the Australian experience. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer. [2018]

9. China pubmed.ncbi.nlm.nih.gov

[Effect of trichostatin A and paclitaxel on the growth and apoptosis of lung adenocarcinoma cell lines]. [2018]

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

Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study. [2021]