Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)

NCT04439123 | Active Not Recruiting Phase 2 Results DMC

• 4 other identifiers: NCI-2020-02980EAY131-YU10CA180820U24CA196172
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II MATCH treatment trial identifies the effects of AZD5363 in patients whose cancer has a genetic change called AKT mutation. AZD5363 may block AKT, which is a protein needed for cancer cell growth. Researchers hope to learn if AZD5363 will shrink this type of cancer or stop its growth.

Conditions

Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Secondary Outcomes (2)

• 6-month Progression-free Survival (PFS) Rate

  Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined

• Progression Free Survival (PFS)

  Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Study Arms (1)

Treatment (capivasertib)

EXPERIMENTAL

Patients receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Capivasertib

Interventions

Capivasertib DRUG

Given PO

Also known as: AZD 5363, AZD-5363, AZD5363, Truqap

Treatment (capivasertib)

Eligibility Criteria

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

You may qualify if:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
• Patients must have an AKT mutation as determined via the MATCH Master Protocol
• Patients with hormone receptor positive, defined as estrogen receptor and/or progesterone receptor \> 1% by immunohistochemistry, AND HER2 negative unresectable breast cancer, with no overexpression by immunohistochemistry (IHC) or amplification by in-situ hybridization, are allowed to continue fulvestrant or an aromatase inhibitor (anastrozole, letrozole, exemestane) with AZD5363 if patient just progressed on this anti-estrogen therapy. Gonadotrophin releasing hormone (GnRH) agonists (such as leuprolide or goserelin) are allowed. For instance, if the last treatment was letrozole plus goserelin, the patient is allowed to continue the letrozole plus goserelin with AZD5363
• NOTE: Selective estrogen receptor modulators (SERMs), such as tamoxifen or toremifene, are not allowed, given concerns about CYPD26 and CYP3A4 metabolism, respectively
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

You may not qualify if:

• Baseline fasting glucose value of \> 8.9 mmol/L or 160 mg/dL (fasting is defined as no calorific intake for at least 8 hours)
• Insulin required for routine diabetic management and control
• More than two oral hypoglycemic medications required for routine diabetic management and control
• Patients must not have known hypersensitivity to AZD5363 or compounds of similar chemical or biologic composition
• Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not eligible for this protocol, as these mutations may lead to limited response due to resistance
• Patients may not have received treatment with another inhibitor of PI3K, AKT or mTOR in the neoadjuvant, adjuvant or metastatic setting with the exception of FDA approved rapalogs. Patients with metastatic cancer, who received PI3K/AKT/mTOR inhibitors on short preoperative window trials (treatment for 4 weeks or less) will be eligible if the treatment was over 6 months prior to registration
• Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

Related Publications (1)

• McCourt CK, Gross J, Kalinsky K, Guan P, McShane LM, Wang V, O'Dwyer PJ, Lahey MT, Maican C, Bu X, Patton D, Harris LN. Comprehensive Molecular and Genomic Analysis of NCI-MATCH Subprotocol Y: Capivasertib in Patients With an AKT1 E17K-Mutated Tumor. JCO Precis Oncol. 2025 Mar;9:e2400614. doi: 10.1200/PO-24-00614. Epub 2025 Mar 28.

  PMID: 40153687 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma; Multiple Myeloma

Interventions

capivasertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Kevin M Kalinsky

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 19, 2020
• Study Start: May 31, 2016
• Primary Completion: November 8, 2019
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 6, 2026
• Results First Posted: August 10, 2021

Record last verified: 2026-05

Locations

US (1)