[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"pik3ca-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:pik3ca-mutation":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,48,73,102],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":36,"lastUpdatePostDateStruct":37,"startDateStruct":40,"completionDateStruct":42,"leadSponsor":44,"locationsCount":47},"100633256","phase-1-study-of-rgt-490-in-patients-with-pik3ca-mutated-advanced-solid-tumors-100633256",false,"NCT07524322","Study of RGT-490 in Patients With PIK3CA-Mutated Advanced Solid Tumors","A Phase 1\u002F1b Open-Label, Multicenter, First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of RGT-490 as a Single Agent in Adult Subjects With Locally Advanced or Metastatic PIK3CA-Mutated Solid Tumors Including HR+\u002FHER2- Breast Cancers","Inclusion Criteria:\n\n* Adults with metastatic or locally advanced, unresectable solid tumors that have progressed on or after at least one available therapy.\n* Presence of one or more documented activating PIK3CA mutation in tumor tissue and\u002For blood.\n* At least 1 measurable lesion or evaluable disease per RECIST v1.1.\n* An ECOG performance status of 0 or 1.\n* Adequate organ function\n\nExclusion Criteria:\n\n* Diabetes mellitus requiring anti-hyperglycemic medication.\n* Prior treatment with PI3Kα inhibitors\n* Symptomatic, untreated, or uncontrolled central nervous system metastases.\n* Receipt of any local or systemic anticancer therapy or investigational anticancer agent within a protocol-defined washout period prior to study treatment.\n* Unresolved clinically significant toxicities from prior anticancer therapy\n* History of a another malignancy within 2 years prior to screening (exception adequately treated cancers).","ALL","18 Years",{"count":19,"type":20},63,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","This is a phase 1\u002F1b, open-label, multicenter study consisting of sequential parts designed to evaluate the safety, tolerability, and effects pharmacokinetic (PK) profile, and antitumor activity of RGT-490, an investigational oral therapy, in adults with locally advanced or metastatic solid tumors including breast cancer.\n\nParticipants enrolled in the study have advanced disease that is not amendable to curative treatment and whose tumors harbor alterations in the PI3KCA gene.",[26,27,28,29,30,31,32,33,34],"Breast Cancer","Ovarian Cancer","Endometrial Cancer","PIK3CA Mutation","HER2- Negative Breast Cancer","Advanced Breast Cancer","Unresectable Solid Tumor","Hormone Receptor Positive Tumor","Cervical Cancer","RECRUITING","2026-06-30",{"date":38,"type":39},"2026-07-02","ACTUAL",{"date":41,"type":20},"2026-06",{"date":43,"type":20},"2028-10",{"name":45,"class":46},"Regor Pharmaceuticals Inc.","INDUSTRY",5,{"id":49,"slug":50,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":53,"acronym":54,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":56,"targetDuration":4,"studyType":21,"phases":58,"briefSummary":60,"conditions":61,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":72},"100591599","phase-3-phase-3-study-of-rly-2608--fulvestrant-vs-capivasertib--fulvestrant-as-treatment-for-locally-advanced-or-metastatic-pik3ca-mutant-hrher2--breast-cancer-100591599","NCT06982521","Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+\u002FHER2- Breast Cancer","A Phase 3 Open-Label Randomized Study Assessing the Efficacy and Safety of RLY-2608 + Fulvestrant Versus Capivasertib + Fulvestrant as Treatment for PIK3CA-mutant Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+\u002FHER2-) Locally Advanced or Metastatic Breast Cancer Following Recurrence or Progression On or After Treatment With a CDK4\u002F6 Inhibitor","ReDiscover-2","Inclusion Criteria:\n\n* Patient has ECOG performance status of 0-1\n* One or more known primary oncogenic PIK3CA mutation(s)\n* Adult females, pre- and\u002For post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 4 weeks prior to randomization and must be willing to continue on it for the duration of the study.\n* Histologically or cytologically confirmed diagnosis of HR+\u002FHER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent\n* Measurable disease per RECIST v1.1 or evaluable bone-only disease.\n* Must have radiological evidence of progression on or after previous treatment for HR+\u002FHER2- ABC with:\n\n  1. At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting\n  2. 1 prior line of CDK4\u002F6 inhibitor therapy in one of the following settings:\n\n     1. CDK4\u002F6 inhibitor + ET in the ABC setting\n     2. CDK4\u002F6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4\u002F6 inhibitor with ET\n     3. Patients who progressed during or within 12 months of completion of adjuvant CDK4\u002F6 inhibitor and after receiving CDK4\u002F6 inhibitor therapy in the advanced setting are considered to have had \\>1 prior line of CDK4\u002F6 inhibitor and are not eligible\n\nExclusion Criteria:\n\n* Prior treatment with any of the following:\n\n  1. CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases\n  2. PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3\u002FAKT\u002FmTOR pathway\n  3. Immunotherapy\n  4. Antibody drug conjugates\n* Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg\u002FdL, or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol\u002Fmol).\n* Clinically significant, uncontrolled cardiovascular disease\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events\n* Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\n* History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients\n* Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K",{"count":57,"type":20},540,[59],"PHASE3","This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+\u002FHER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4\u002F6 inhibitor.",[29,30,33,26,62,31],"Metastatic Breast Cancer","2026-06-10",{"date":65,"type":39},"2026-06-11",{"date":67,"type":39},"2025-08-26",{"date":69,"type":20},"2031-12-31",{"name":71,"class":46},"Relay Therapeutics, Inc.",192,{"id":74,"slug":75,"hasResults":11,"nctId":76,"briefTitle":77,"officialTitle":78,"acronym":4,"eligibilityCriteria":79,"healthyVolunteers":11,"sex":16,"minAge":80,"maxAge":4,"enrollmentInfo":81,"targetDuration":4,"studyType":21,"phases":83,"briefSummary":85,"conditions":86,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":63,"lastUpdatePostDateStruct":94,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":101},"100576793","phase-2-a-phase-2-study-of-mutant-selective-pi3k-inhibitor-rly-2608-in-adults-and-children-with-pik3ca-related-overgrowth-spectrum-and-malformations-driven-by-pik3ca-mutation-the-reinspire-study-100576793","NCT06789913","A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation (The ReInspire Study)","A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation","Key Inclusion Criteria:\n\n* The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA classification.\n* One or more documented activating PIK3CA mutation(s) that are targeted by selective PI3Kα inhibitors in lesional tissue and\u002For cell-free DNA from the lesion or blood. Some participants may be eligible without a documented PIK3CA mutation, with the sponsor's approval, as long as no other genetic driver has been documented.\n* Lansky (\\\u003C16 yo) or Karnofsky (≥16 yo) performance status of ≥50.\n* Agree to provide archived lesional fluid and\u002For tissue or be willing to undergo pretreatment lesional biopsy (if considered safe and medically feasible) to assess PIK3CA status.\n\nKey Exclusion Criteria:\n\n* Known hypersensitivity to RLY-2608.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events\n* Clinically significant, uncontrolled cardiovascular disease\n* Received disease-directed therapy prior to the first dose of study drug:\n\n  1. Systemic therapy or antibody within 5 half-lives of the therapy.\n  2. Local therapy including radiation, surgery, or other procedures within 28 days; lesion(s) must have demonstrated progression after the procedure.","2 Years",{"count":82,"type":20},277,[84],"PHASE2","This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, zovegalisib (RLY-2608), in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations driven by PIK3CA mutation. Part 1 is a dose selection, Part 2 is a basket design with exploratory single-arm cohorts for various subpopulations of participants, and Part 3 is randomized, double-blinded study vs placebo.",[87,88,89,29,90,91,92,93],"PIK3CA-Related Overgrowth Spectrum (PROS)","Lymphatic Malformations","Vascular Malformations","CLOVES Syndrome","Klippel Trenaunay Syndrome","Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)","Vascular Anomalies",{"date":95,"type":39},"2026-06-12",{"date":97,"type":39},"2025-06-13",{"date":99,"type":20},"2031-10",{"name":71,"class":46},34,{"id":103,"slug":104,"hasResults":11,"nctId":105,"briefTitle":106,"officialTitle":106,"acronym":4,"eligibilityCriteria":107,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":108,"targetDuration":4,"studyType":21,"phases":110,"briefSummary":111,"conditions":112,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":115,"lastUpdatePostDateStruct":116,"startDateStruct":118,"completionDateStruct":120,"leadSponsor":122,"locationsCount":123},"100455889","phase-1-first-in-human-study-of-mutant-selective-pi3k-inhibitor-rly-2608-as-a-single-agent-in-patients-with-advanced-solid-tumors-and-in-combination-with-endocrine-therapy---a-cdk46-or-cdk4-inhibitor-in-patients-with-advanced-solid-tumors-or-advanced-breast-cancer-100455889","NCT05216432","First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +\u002F- a CDK4\u002F6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer","Key Inclusion Criteria\n\nPatient has ECOG performance status of 0-1\n\nOne or more documented primary oncogenic PIK3CA mutation(s) in blood and\u002For tumor per local assessment\n\nOther potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment.\n\nPart 1 \\[Escalation\\] - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 \\[Expansion\\] - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively.\n\nKey Inclusion for RLY-2608 Single Agent Arm\n\n* \\[For Part 1: Escalation\\]: Evaluable disease per RECIST v1.1\n* \\[For Part 2: Expansion\\]: Measurable disease per RECIST v1.1\n* Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy.\n* Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor\n* Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types:\n\nGroup 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations In addition, the SRC (with Sponsor approval) may choose to open additional group(s) of 20 participants to study the clinical activity, safety, and PK\u002FPD with other specified solid tumor types.\n\nKey Inclusion for Combination Arms:\n\n* Doublet combination arms \\[Part 1 and Part 2\\]: Evaluable disease per RECIST v1.1\n* Triplet combination arms:\n* \\[Part 1 and Part 2 Dose Expansion, Group 1\\]: Evaluable disease per RECIST.\n* \\[Part 2 Dose Expansion, Group 2\\]: Measurable disease per RECIST. Bone-only lytic or lytic\u002Fblastic disease with at least 1 measurable soft-tissue component per RECIST may be eligible.\n* \\[For Part 1 and Part 2\\]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy and must have initiated treatment with a gonadotropin-releasing hormone (GnRH) agonist at least 4 weeks prior to start of study drug with continuation of GnRH agonist for the duration of study treatment (GnRH agonist recommended for males).\n* Had previous treatment for breast cancer with: \\[Does not apply to triplet combination arms, Part 2 Dose Expansion, Group 2\\]:\n\n  1. ≤1 line of chemotherapy in the metastatic setting\n  2. ≥1 CDK4\u002F6 inhibitor in either the adjuvant and\u002For metastatic setting\n  3. ≥1 antiestrogen therapy in either adjuvant and\u002For metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and\n  4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1\u002F2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment\n\n\\[For double combination arm; Part 2 Dose Expansion, Group 2\\]: Received prior treatment with a PI3Kα, AKT, or mTOR inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and\u002For life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.\n\n\\[For triple combination arms; Part 1 dose escalation\\]: Participants who had previous treatment for breast cancer with PI3Kα, AKT, mTOR inhibitors and discontiuned due to participant\u002Fphysician decision, intolerance, or disease progression will be considered.\n\n\\[For triple combination arms, Part 2 Dose Expansion, Group 2\\]: Participants must be intolerant to or have declined standard therapy for locally advanced or metastatic HR+\u002FHER2- PIK3CA-mutated breast cancer. Prior endocrine therapy and CDK4\u002F6inhibitors are allowed as follows:\n\n1. Participants must have progressed during (neo)adjuvant endocrine therapy or within12 months of completing (neo)adjuvant endocrine therapy with an AI or tamoxifen.\n2. If a CDK4\u002F6 inhibitor was included as part of (neo)adjuvant therapy, disease must have recurred\u002Fprogressed \\>12 months after completion of the CDK4\u002F6 inhibitor portion of (neo)adjuvant therapy\n\nKey Exclusion Criteria\n\nPrior treatment with:\n\n1. PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation).\n2. Immune checkpoint inhibitors.\n3. Triplet combinations RLY-2608 + CDK4 or CDK4\u002F6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only:\n\ni. Prior systemic chemotherapy or antibody drug conjugate for locally advanced or metastatic disease. ii. Prior CDK2, CDK4, or CDK4\u002F6 inhibitor as treatment for locally advanced or metastatic disease.\n\niii. Prior treatment with fulvestrant or any selective ER degrader, with the exception of patients who have received fulvestrant or any selective ER degrader as part of neoadjuvant therapy only and with treatment duration ≤6 months.\n\nType 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg\u002FdL and glycosylated hemoglobin (HbA1c) ≥7.0%.\n\nHistory of allergy or hypersensitivity to any components or excipients of PI3K inhibitors. For combination arms only: allergy or hypersensitivity to any components or excipients of fulvestrant, palbociclib, ribociclib, and\u002For PF-07220060 as appropriate for the combination.\n\nPast medical history of or ongoing ILD, or pneumonitis requiring intervention. Participants with past history of resolved Grade 1 pneumonitis may be considered, except in triple combination arms.\n\nThe following cardiac criteria:\n\n* Mean resting corrected QT interval (QTc) \\>460 msec\n* For triple combination arm with ribociclib: Mean QTcF ≥450 msec (this is what we confirmed is shown in the redacted version of the protocol.\n\nCNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms",{"count":109,"type":20},930,[23],"This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and\u002For tumor per local assessment. The study will evaluate RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors. It will also evaluate RLY-2608 in combination RLY-2608 + fulvestrant and in triple combination RLY-2608 + fulvestrant + CDK4\u002F6 inhibitor (palbociclib or ribociclib) or CDK4 inhibitor (PF-07220060) for patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2 parts: a dose escalation (Part 1) and a dose expansion (Part 2).",[29,113,114,26,62,31,32],"Solid Tumor, Adult","HER2-negative Breast Cancer","2025-09-17",{"date":117,"type":39},"2025-09-22",{"date":119,"type":39},"2021-12-08",{"date":121,"type":20},"2027-04-30",{"name":71,"class":46},37]