Trial Outcomes & Findings for Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K) (NCT NCT06400251)

Last Updated: 2025-11-20

Results Overview

ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with 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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

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

Results posted on

2025-11-20

Participant Flow

Subprotocol Z1K was activated on July 25, 2019. Thirty-five patients were enrolled on EAY131-Z1K between August 8, 2019, and November 11, 2020. All patients were enrolled on the basis of the outside lab assay results.

Patients with tumors harboring E17K mutations in AKT1, 2, and 3, as well as Q79K and L52R mutations in AKT1, were eligible for sub-protocol Z1K. The mutation status was determined by an NCI-MATCH approved laboratory for all patients in this arm, they had to be confirmed by the NCI-MATCH central assay to be included in primary analysis.

Participant milestones

Participant milestones
Measure	Treatment (Ipatasertib) Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Overall Study STARTED	35
Overall Study Started Protocol Therapy	34
Overall Study Eligible and Treated	32
Overall Study Eligible, Treated and Mutation Status Confirmed	29
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Ipatasertib) Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Overall Study Never Start Protocol Therapy	1
Overall Study Ineligible	2
Overall Study Mutation Status Not Confirmed	3
Overall Study Disease Progression	25
Overall Study Adverse Event	1
Overall Study Complicating Disease	1
Overall Study Physician Decision	2

Baseline Characteristics

Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Ipatasertib) n=29 Participants Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Age, Continuous	63 years
Sex: Female, Male Female	27 Participants
Sex: Female, Male Male	2 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) White	22 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants

PRIMARY outcome

Timeframe: 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

Population: Eligible, treated and mutation status confirmed

Outcome measures

Outcome measures
Measure	Treatment (Ipatasertib) n=29 Participants Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Objective Response Rate (ORR)	24.1 percentage of participants Interval 11.9 to 40.6

SECONDARY outcome

Timeframe: 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

Population: Eligible, treated and mutation status confirmed

Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression 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. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.

Outcome measures

Outcome measures
Measure	Treatment (Ipatasertib) n=29 Participants Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
6-month Progression Free Survival (PFS)	46.8 percentage of participants Interval 30.9 to 61.2

SECONDARY outcome

Timeframe: 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

Population: Eligible, treated and mutation status confirmed

PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression 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. Please refer to the protocol for detailed definitions of disease progression.

Outcome measures

Outcome measures
Measure	Treatment (Ipatasertib) n=29 Participants Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Progression Free Survival	5.5 months Interval 3.6 to 12.9

Adverse Events

Treatment (Ipatasertib)

Serious events: 13 serious events

Other events: 27 other events

Deaths: 26 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ipatasertib) n=34 participants at risk Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Blood and lymphatic system disorders Anemia	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Cardiac disorders Cardiac arrest	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
General disorders Fatigue	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Skin and subcutaneous tissue disorders Rash maculo-papular	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Diarrhea	8.8% 3/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Nausea	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Vomiting	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Infections and infestations Skin infection	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Alanine aminotransferase increased	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Alkaline phosphatase increased	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Aspartate aminotransferase increased	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Lymphocyte count decreased	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Platelet count decreased	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Metabolism and nutrition disorders Hyperglycemia	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Vascular disorders Thromboembolic event	2.9% 1/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).

Other adverse events

Other adverse events
Measure	Treatment (Ipatasertib) n=34 participants at risk Patients receive ipatasertib 400 mg PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.
Blood and lymphatic system disorders Anemia	14.7% 5/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
General disorders Fatigue	17.6% 6/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Skin and subcutaneous tissue disorders Dry skin	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Skin and subcutaneous tissue disorders Rash maculo-papular	8.8% 3/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Abdominal pain	8.8% 3/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Diarrhea	67.6% 23/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Dry mouth	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Dyspepsia	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Mucositis oral	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Nausea	35.3% 12/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Gastrointestinal disorders Vomiting	14.7% 5/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Alanine aminotransferase increased	14.7% 5/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Alkaline phosphatase increased	11.8% 4/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Aspartate aminotransferase increased	20.6% 7/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Creatinine increased	17.6% 6/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Platelet count decreased	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations Weight gain	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Investigations White blood cell decreased	11.8% 4/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Metabolism and nutrition disorders Anorexia	17.6% 6/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Metabolism and nutrition disorders Dehydration	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Metabolism and nutrition disorders Hyperglycemia	26.5% 9/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Metabolism and nutrition disorders Hypokalemia	8.8% 3/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Metabolism and nutrition disorders Hyponatremia	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Nervous system disorders Dizziness	5.9% 2/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).
Nervous system disorders Dysgeusia	8.8% 3/34 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Thirty-four patients were included in the toxicity analysis (excluding one who did not receive treatment).

Additional Information

Study Statistician

ECOG-ACRIN Cancer Research Group

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60