Inavolisib for PIK3CA Mutated Advanced Endometrial Cancer: MITO END-4

NCT07522697 | Not Yet Recruiting Phase 2

• 2 other identifiers: MITO END-4 2025-522981-61-002025-522981-61-00
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

MITO END-4 is a prospective, single arm, multicentric phase II trial aiming to assess whether Inavolisib is effective in the treatment of advanced endometrial carcinoma with pathogenic PIK3CA mutation. Approximately 48 patients with PIK3CA mutation will be overall enrolled in the study.

Conditions

Endometrial Cancer

Keywords

endometrial cancer; PIK3CA; inavolisib; phase II trial

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  a complete response (CR) or partial response (PR) by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria.

  Every 8 (±1) weeks during the first 2 years, every 12 (±1) weeks therafter, from enrollment until disease progression (up to 48 months).

Secondary Outcomes (8)

• progression-free survival (PFS) at 6 months

  from enrollment to 6 months

• disease-control rate (DCR)

  from enrollment until disease progression (up to 48 months)

• duration of response (DoR)

  from enrollment until disease progression (up to 48 months)

• response rate in patients with different PIK3CA mutations

  Every 8 (±1) weeks during the first 2 years, every 12 (±1) weeks therafter, from enrollment until disease progression (up to 48 months).

• response rate in patients with PIK3CA mutations and PTEN intact

  Every 8 (±1) weeks during the first 2 years, every 12 (±1) weeks therafter, from enrollment until disease progression (up to 48 months).

Other Outcomes (2)

• response rate to inavolisib in correlation with molecular characteristics of the tumour

  Every 8 (±1) weeks during the first 2 years, every 12 (±1) weeks therafter, from enrollment until disease progression (up to 48 months).

• correlation of identified mutations in tumor tissue and blood during therapy

  from enrollment until disease progression (up to 48 months).

Study Arms (1)

Inavolisib

EXPERIMENTAL

The planned starting dose for inavolisib will be 9 mg PO QD taken on Days 1-28 of each 28-day cycle. Dosing will continue until disease progression, unacceptable toxicity, or death. Specifically, the recommended starting dosage of inavolisib for patients with moderate renal impairment (CrCL 30 to \<60 mL/min) is 6 mg orally once daily.

Drug: Inavolisib

Interventions

Inavolisib DRUG

The planned starting dose for inavolisib will be 9 mg PO QD taken on Days 1-28 of each 28-day cycle. Dosing will continue until disease progression, unacceptable toxicity, or death. Specifically, the recommended starting dosage of inavolisib for patients with moderate renal impairment (CrCL 30 to \<60 mL/min) is 6 mg orally once daily.

Inavolisib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to any study specific procedures.
• Female, age ≥ 18 years at time of signing informed consent.
• Patients with histologically or cytologically confirmed diagnosis of advanced, recurrent or metastatic endometrial carcinoma (endometrioid, serous, clear cell, carcinosarcoma or mixed histology).
• Biomarker eligibility: valid results from testing of tumor tissue documenting PIK3CA mutations listed below (a-m); however, activating PIK3CA mutations not listed may also be included, capped at 20% of the study population.
• H1047D/I/L/N/P/Q/R/T/Y G1049A/C/D/R/S E545A/D/G/K/L/Q/R/V E453A/D/G/K/Q/V E542A/D/G/K/Q/R/V K111N/R/E Q546E/H/K/L/P/R G106A/D/R/S/V N345D/H/I/K/S/T/Y G118D C420R R88Q M1043I/T/V
• Data from the reports indicating the pertinent PIK3CA mutation as well as the status of PTEN gene, and relative variant of allelic frequency (VAF) for each altered gene must be available upon enrollment. Local test results reported from tumor tissue should be from the patient's locally advanced or metastatic disease state whenever possible. Specifically, the detection of PIK3CAm combined with knowledge of PTEN molecular status is mandatory for the screening.
• All patients are required to submit a paraffin embedded block from the primary surgery/biopsy (chemotherapy - naive patients) and a freshly collected pre-treatment blood samples. A quality control analysis of samples will be performed by the Sponsor, before patient's enrollment. Only patients with adequate tumor sample will be enrolled.
• Patients must have progressed after or during a platinum based-chemotherapy with or without immunotherapy in any setting. Specifically, patients receiving previous platinum-based chemotherapy in the neoadjuvant or adjuvant setting must have progressed within 6 months of last platinum therapy.
• Patients must have received no more than 4 previous systemic therapy for endometrial cancer. Specifically, endocrine therapies, maintenance with PARP inhibitor or selinexor are not counted as a systemic line of therapy.
• At least 1 measurable target lesion according to RECIST 1.1
• Patients must have a life expectancy ≥ 16 weeks.
• ECOG performance status of 0 to 1 within 28 days of enrollment.
• Documented markers such as mismatch repair (MMR) status, hormone receptors (estrogen and progesterone receptors) and p53 status according to molecular or immunohistochemical classification of EC.
• Patient must be able to take oral medications.
• Patients must have normal organ and bone marrow function measured as defined below:

You may not qualify if:

• Endometrial tumors with the following histologies: squamous carcinomas, sarcomas.
• Prior treatment in locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K/AKT/mTOR pathway.
• Any history of Type 1 diabetes and Type 2 diabetics patients with fasting blood glucose \>140 and HbA1C ≥6.5%, and/or those that require 2 or more anti-diabetic agents should be excluded.
• Subjects known to be positive for Human Immunodeficiency Virus (HIV).
• Patients with known active hepatitis (i.e. Hepatitis B or C)
• Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Patients unable to swallow orally administered medication and patients with gastrointestinal malabsorption or any other condition that may interfere with absorption of Inavolisib.
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
• Major surgery within 28 days weeks of starting study treatment and patients must have recovered from any effects of major surgery. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
• Minor surgical procedures \< 7 days prior to first dose of study treatment.
• Patients must have sufficiently recovered from surgery, including adequate wound healing.
• Known untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (i.e. without evidence of progression) for at least 4 weeks by repeat imaging (Note: The repeat imaging should be performed during study Screening.), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study intervention.
• Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS).
• Participation in another clinical study with an investigational drug product within 4 weeks before randomization.

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

National Cancer Institute of Napoli, Division of Medical Oncology - Uro-Gynecology Department

Naples, 80131, Italy

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Interventions

inavolisib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Anna Passarelli

  National Cancer Institute, Naples

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Lucia Iacovino

CONTACT

+39 08117770692; marialucia.iacovino@istitutotumori.na.it

Anna Passarelli

CONTACT

anna.passarelli@istitutotumori.na.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single agent therapy with Inavolisib

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 13, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

IT (1)