Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202402608766452 Date of Approval: 01/02/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer
Official scientific title A phase III, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Inavolisib in combination with Phesgo versus placebo in combination with Phesgo as maintenance therapy after first line induction therapy in participants with PIK3CA‐mutated HER2‐positive locally advanced or metastatic breast cancer
Brief summary describing the background and objectives of the trial This study will evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for SC use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive ABC. - Primary Objective: To demonstrate PFS superiority of inavolisib in combination with Phesgo over placebo in combination with Phesgo - Key secondary objective: To evaluate OS of inavolisib in combination with Phesg compared to placebo in combination with Phesgo
Type of trial RCT
Acronym (If the trial has an acronym then please provide) INAVO122
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/04/2024
Actual trial start date
Anticipated date of last follow up 31/10/2028
Actual Last follow-up date
Anticipated target sample size (number of participants) 4
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Maintenance Therapy Inavolisib plus Phesgo Drug: Inavolisib Participants will receive an inavolisib tablet to be taken orally (PO), once a day (QD), on Days 1-21 of each 21-day cycle, beginning on Day (D) 1 of Cycle (C) 1 of maintenance treatment. Drug: Phesgo Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle. Drug: Optional Endocrine Therapy of Investigator's Choice Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information. Other Name: NIMP Drug: Inavolisib Participants will receive an inavolisib tablet to be taken orally (PO), once a day (QD), on Days 1-21 of each 21-day cycle, beginning on Day (D) 1 of Cycle (C) 1 of maintenance treatment. Drug: Phesgo Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle. Drug: Optional Endocrine Therapy of Investigator's Choice Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information. Other Name: NIMP Drug: Inavolisib Participants will receive an inavolisib tablet to be taken orally (PO), once a day (QD), on Days 1-21 of each 21-day cycle, beginning on Day (D) 1 of Cycle (C) 1 of maintenance treatment. Drug: Phesgo Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle. Drug: Optional Endocrine Therapy of Investigator's Choice Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information. Other Name: NIMP 2
Control Group Maintenance Therapy Placebo plus Phesgo Drug: Phesgo Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle. Drug: Placebo Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment. Drug: Optional Endocrine Therapy of Investigator's Choice Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information. Other Name: NIMP Drug: Phesgo Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle. Drug: Placebo Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment. Drug: Optional Endocrine Therapy of Investigator's Choice Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information. Other Name: NIMP Drug: Phesgo Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle. Drug: Placebo Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment. Drug: Optional Endocrine Therapy of Investigator's Choice Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information. Other Name: NIMP 2 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 - Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection - Confirmation of HER2 biomarker eligibility based on valid results from central testing of tumor tissue documenting HER2-positivity - Confirmation of PIK3CA-mutation biomarker eligibility based on valid results from central testing of tumor tissue documenting PIK3CA-mutated tumor status - Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of >= 6 months - LVEF (left ventricular ejection fraction) of at least 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) - Adequate hematologic and organ function prior to initiation of study treatment - Prior treatment in the 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 prior systemic non-hormonal anti-cancer therapy for locally advanced or metastatic HER2-positive breast cancer prior to initiation of induction therapy - History or active inflammatory bowel disease - Disease progression within 6 months of receiving any HER2-targeted therapy - Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes - Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis - Symptomatic active lung disease, including pneumonitis or interstitial lung disease - Any history of leptomeningeal disease or carcinomatous meningitis - Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1 - Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition - Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/11/2023 Kenyatta National Hospital University of Nairobi
Ethics Committee Address
Street address City Postal code Country
Nairobi Nairobi 00202 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Investigator-Assessed Progression-Free Survival (PFS) [ Time Frame: Up to approximately 40 months ] Time Frame Up to approximately 40 months
Secondary Outcome - Overall Survival (OS) [ Time Frame: Up to approximately 111 months ] - Investigator-Assessed Objective Response Rate (ORR) [ Time Frame: Up to approximately 111 months ] - Investigator-Assessed Duration of Response (DOR) [ Time Frame: Up to approximately 111 months ] - Investigator-Assessed Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 111 months ] - Investigator-Assessed PFS2 [ Time Frame: Up to approximately 111 months ] - Mean and Mean Changes from Baseline Score in Function and Health-Related Quality of Life (HRQoL) [ Time Frame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit every 6 months (up to 111 months). Each cycle is 21 days. ] Assessed through the use of the Functional (Role, Physical) and Global Health Status (GHS)/Quality of Life (QoL) scales of the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) - Percentage of Participants with Adverse Events [ Time Frame: Day 1 until 30 days after the final dose of study treatment (up to approximately 111 months). Each cycle is 21 days. ] - Plasma Concentration of Inavolisib at Specified Timepoints [ Time Frame: Day 1 of Cycles 1 and 4. Each cycle is 21 days. ] Indicated above in the outcome section
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Nairobi Institute of Tropical and Infectious Diseases P.O. BOX 19676-00202 Nairobi City 00202 Kenya
Uganda Cancer Institute Upper Mulago Hill Kampala Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Faith Wanjau faith.wanjau@roche.com +25472744262 The Atrium, 6th Floor, Chaka Road, Off Lenana Road
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Clinical Operations Lead
Role Name Email Phone Street address
Principal Investigator Sitna Ali Mwanzi sitna.ali@gmail.com +254717333452 UNIVERSITY OF NAIROBI INSTITUTE OF TROPICAL AND INFECTIOUS DISEASES
City Postal code Country Position/Affiliation
Nairobi 00200 Kenya Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Constantina Theodosopoulos constantina.theodosopoulos@roche.com +447770620748 Roche Products Ltd 6 Falcon Way, Shire Park, Welwyn Garden City AL7 1TW, United Kingdom
City Postal code Country Position/Affiliation
Welwyn Garden City AL7 1TW United Kingdom Clinical Operations Lead
Role Name Email Phone Street address
Principal Investigator Nixon Niyonzima nixon.niyonzima@uci.or.ug +256755677395 Upper Mulago Hill
City Postal code Country Position/Affiliation
Kampala Uganda Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes There is a plan to share IPD. Plan description: -Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). -Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). --For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).There are no publications yet Clinical Study Report Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
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