Sapanisertib + Serabelisib + Paclitaxel for Endometrial Cancer

Recruiting at 18 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Faeth Therapeutics

Must be taking: Platinum chemotherapy, Checkpoint inhibitors

Must not be taking: Strong CYP3A4 inhibitors, PPIs

Disqualifiers: CNS metastases, Active malignancy, Cardiovascular impairment, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three treatments—sapanisertib, serabelisib, and paclitaxel—specifically for advanced or recurrent endometrial cancer. The goal is to determine the safety and effectiveness of these drugs when used together. It suits those with endometrioid endometrial cancer that cannot be treated with surgery or radiation and who have tried at least one other treatment, such as chemotherapy. Participants should also have a specific gene change in the PI3K/AKT/mTOR pathway that affects cell growth. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking strong CYP3A4 inhibitors or inducers, and strong CYP1A2 inhibitors or inducers, at least 7 days before starting the study. You also cannot take PPIs or certain antacids during the study.

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

Research has shown that the combination of sapanisertib and serabelisib with paclitaxel has generally been well-tolerated. One study found this combination safe, with no unexpected side effects. Patients mostly experienced common side effects like nausea and tiredness, typical for cancer treatments. Safety results from earlier studies suggest that this treatment is reasonably safe. However, monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometrial cancer?

Unlike the standard treatments for endometrial cancer, which often include surgery, radiation, and chemotherapy, Sapanisertib and Serabelisib target specific pathways involved in cancer cell growth. Sapanisertib works by inhibiting mTOR, a protein that helps cancer cells grow and survive, while Serabelisib targets the PI3K pathway, another critical player in cancer cell proliferation. This dual-action approach could potentially make these drugs more effective at stopping cancer progression and may offer a more precise treatment option compared to traditional chemotherapy. Researchers are particularly excited because these targeted therapies might lead to better outcomes with fewer side effects for patients.

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

Studies have shown that using the drugs sapanisertib, serabelisib, and paclitaxel together can help treat certain cancers. In this trial, participants will receive a combination of sapanisertib and serabelisib administered orally, along with paclitaxel administered intravenously. Research indicates that this combination is not only safe but also showed promising results in early trials, especially where few treatment options exist. Sapanisertib and serabelisib target specific parts of cancer cells, potentially stopping their growth. Paclitaxel, a well-known chemotherapy drug, prevents cancer cells from dividing. Together, these drugs might offer a strong approach to treating advanced or recurring endometrial cancer. These findings suggest that this treatment could be effective for patients with this condition. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for women with advanced or recurrent endometrial cancer that can't be treated with surgery or radiation. They must have had 1-3 prior treatments, a specific gene alteration, and be in good physical condition. Participants need at least one measurable tumor and agree to use contraception if not postmenopausal or surgically sterile.

Inclusion Criteria

My cancer's gene alteration status for the PI3K/AKT/mTOR pathway is known.

I am fully active or can carry out light work.

I have at least one tumor that can be measured.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sapanisertib and serabelisib (PIKTOR) orally and paclitaxel intravenously

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Sapanisertib
• Serabelisib

Trial Overview

The study tests the combination of two drugs, Sapanisertib and Serabelisib (PIKTOR), with Paclitaxel on patients with endometrial cancer. It's an open-label Phase 2 trial where all participants receive the same treatment to assess its effectiveness and safety.

How Is the Trial Designed?

Group I: sapanisertib and serabelisib (PIKTOR) with paclitaxel Experimental Treatment 3 Interventions

Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) administered orally and paclitaxel administered intravenously.

Who Is Running the Clinical Trial?

Faeth Therapeutics

Lead Sponsor

Trials

4

Recruited

170+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Published Research Related to This Trial

The combination of paclitaxel and carboplatin showed a promising response rate in patients with high-risk endometrial cancer, achieving complete responses in 45.5% and partial responses in 27.3% of the 11 evaluable patients.

However, the treatment was associated with significant toxicity, with 49.2% of patients experiencing severe leukopenia and 90.5% experiencing severe neutropenia, indicating the need for supportive care in a substantial number of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of paclitaxel and carboplatin in patients with endometrial cancer]. Nakamura, T., Onishi, Y., Yamamoto, F., et al.[2015]

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 II study involving 67 patients with advanced or recurrent endometrial carcinoma, the PI3K inhibitor pilaralisib showed a low objective response rate of only 6.0%, indicating minimal antitumor activity.

Pilaralisib was generally well-tolerated, with the most common treatment-related side effects being rash (40.3%), diarrhea (37.3%), and fatigue (28.4%), suggesting a favorable safety profile despite limited efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. Matulonis, U., Vergote, I., Backes, F., et al.[2022]

In a phase II study involving 53 patients with persistent or recurrent carcinosarcoma of the uterus, paclitaxel demonstrated moderate clinical activity, with an overall response rate of 18.2%, including both complete and partial responses.

The most common side effect observed was neutropenia, indicating that while paclitaxel can be effective, it also carries risks that need to be monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel in the treatment of carcinosarcoma of the uterus: a gynecologic oncology group study. Curtin, JP., Blessing, JA., Soper, JT., 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 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, 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 study of 48 patients with high-risk stage III and IV endometrial cancer, the combination of paclitaxel and carboplatin (TC) after complete tumor resection resulted in a 3-year overall survival rate of 56% and a median overall survival of 47 months.

The treatment was well tolerated, with 90% of patients completing all planned cycles, and a median time to disease progression of 13 months, indicating that TC is an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Sovak, MA., Hensley, ML., Dupont, J., et al.[2015]

In a study of 63 patients with advanced or recurrent endometrial cancers, the combination of carboplatin and paclitaxel showed high response rates, with 78% in advanced nonpapillary serous cancers and 60% in advanced papillary serous cancers.

The treatment demonstrated manageable toxicity, primarily hematologic, and resulted in significant survival outcomes, including a median failure-free survival of 23 months for advanced nonpapillary serous cancers and a 62% overall survival rate at 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. Hoskins, PJ., Swenerton, KD., Pike, JA., et al.[2022]

In a phase 2 study involving 241 patients with advanced endometrial cancer, the combination of sapanisertib and paclitaxel showed a median progression-free survival (PFS) of 5.6 months compared to 3.7 months for paclitaxel alone, although the primary endpoint was not statistically significant (p = 0.139).

The combination treatment resulted in a higher rate of grade ≥ 3 treatment-emergent adverse events (89.5% for paclitaxel+sapanisertib vs. 54.0% for paclitaxel alone), indicating increased toxicity, but it was still considered manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer. Han, SN., Oza, A., Colombo, N., et al.[2023]

In a study of 30 patients with advanced or recurrent endometrial cancer, paclitaxel demonstrated a response rate of 35.7%, with 14.3% achieving complete responses and 21.4% showing partial responses.

While paclitaxel was effective, it also caused significant side effects, including severe leukopenia in 18 patients and gastrointestinal toxicity in 5, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Ball, HG., Blessing, JA., Lentz, SS., et al.[2015]

In a phase 3 trial involving 827 patients with advanced endometrial cancer, the combination of lenvatinib and pembrolizumab (LEN+PEMBRO) showed significant improvements in efficacy compared to the treatment of physician's choice (TPC), indicating it is a promising treatment option.

Health-related quality of life (HRQoL) assessments revealed that while LEN+PEMBRO had advantages in certain symptoms like dyspnoea and body image, TPC was favored for pain and appetite loss, suggesting that LEN+PEMBRO offers a favorable overall benefit/risk profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice. Lorusso, D., Colombo, N., Herraez, AC., et al.[2023]

Citations

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Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel and ...

This is a Phase 2, multicenter, open-label, single-arm study to evaluate the efficacy and safety of sapanisertib and serabelisib (PIKTOR) with paclitaxel in ...

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pubmed.ncbi.nlm.nih.gov

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Phase I dose escalation study of dual PI3K/mTOR ...

The combination of sapanisertib, serabelisib, and paclitaxel was safe and generally well tolerated. Preliminary efficacy was remarkable in an area of unmet ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0090825823014853

A randomized phase 2 study of sapanisertib in combination ...

This randomized, phase 2, 4-arm study assessed the efficacy and safety of sapanisertib alone, or in combination with paclitaxel or TAK-117, versus paclitaxel ...

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ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.5569

Final results of phase 1 evaluation of the safety and clinical ...

Overall, the combination of sapanisertib, serabelisib, and paclitaxel was safe and efficacious throughout the first 4 cohorts.

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NCT02725268 | A Study of Sapanisertib, Combination ...

Sapanisertib is being evaluated as a single agent and in combination with paclitaxel or MLN1117 to treat women with advanced, recurrent, or persistent ...

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ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15134

Serabelisib, sapanisertib (PIKTOR) and paclitaxel

The Phase 1 study combined the targeted PI3K-alpha and mTOR inhibitors serabelisib and sapanisertib (PIKTOR) with paclitaxel showing reasonable safety and ...

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Results of a phase Ib trial evaluating the safety and clinical ...

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