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115 Diseases | | 4 Products |
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10 Trials |  |
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- paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
EVALUATION OF PAXALISIB IN GBM AGILE PHASE 3 REGISTRATION PLATFORM TRIAL FOR NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA (Hall A3) - Nov 22, 2024 - Abstract #SNO2024SNO_1794;
P2/3
CONCLUSION Paxalisib did not show survival benefit over cumulative control in final primary analysis; additional secondary analyses are being considered. GBM AGILE continues to rapidly and efficiently assess therapies in ND and RD glioblastoma.
- | paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
New P1 trial, Metastases: Paxalisib Plus Olaparib or Pembrolizumab/Chemotherapy in Advanced Breast Cancer (EUDRACT) - Nov 8, 2024
P1, N=24, Not yet recruiting, Sponsor: Kazia Therapeutics
- paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
Multi-Center Phase I Study of Concurrent Paxalisib and Radiation Therapy (RT) In Patients With Solid Tumor Brain Metastases (BM) or Leptomeningeal Metastases (LM) Harboring PI3K Pathway Alterations (General Assembly C) - Nov 7, 2024 - Abstract #SNO2024SNO_247;
- | Herceptin (trastuzumab) / Roche, paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
Enrollment closed: GDC-0084 in Combination with Trastuzumab for Patients with HER2-Positive Breast Cancer Brain Metastases (clinicaltrials.gov) - Nov 5, 2024
P2, N=47, Active, not recruiting, Sponsor: Dana-Farber Cancer Institute
GBM AGILE continues to rapidly and efficiently assess therapies in ND and RD glioblastoma. Recruiting --> Active, not recruiting
- Herceptin (trastuzumab) / Roche, paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
Final results of a phase II trial evaluating paxalisib with trastuzumab for patients (pts) with HER2 positive metastatic breast cancer with active brain metastases. (Halls 2-3) - Nov 1, 2024 - Abstract #SABCS2024SABCS_2030;
- Immunotherapy and PI3K/mTOR inhibition combination to mediate metastasis and immunotherapy resistance in triple-negative breast cancer (Halls 2-3) - Nov 1, 2024 - Abstract #SABCS2024SABCS_1240;
- | Journal: Construction of Anthocyanin Biosynthesis System Using Chalcone as a Substrate in Lactococcus lactis NZ9000. (Pubmed Central) - Jul 29, 2024
This is the first time that a five-step metabolic pathway has been developed for anthocyanin biosynthesis in probiotic L. lactis NZ9000. This work lays the groundwork for novel anthocyanin production by a process involving the placement of several biosynthesis genes under the control of a gene cluster.
- | riluzole / Generic mfg., NV-128 / MEI, ME-344 / MEI
Journal: Correlation of disulfidptosis and periodontitis: New insights and clinical significance. (Pubmed Central) - Jul 28, 2024
This work lays the groundwork for novel anthocyanin production by a process involving the placement of several biosynthesis genes under the control of a gene cluster. SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis.
- paxalisib (GDC-0084) / Kazia, SoVarGen
Multi-Center Phase I Study of Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases (BM) or Leptomeningeal Metastases (LM) Harboring PI3K Pathway Mutations (Room 151) - Jul 13, 2024 - Abstract #ASTRO2024ASTRO_2711;
- ||| paxalisib (GDC-0084) / Kazia, SoVarGen, pimasertib (AS703026) / Day One Biopharma
Enrollment open, Trial initiation date: Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer (clinicaltrials.gov) - Jul 11, 2024
P1/2, N=82, Recruiting, Sponsor: Australian & New Zealand Children's Haematology/Oncology Group
SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis. Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Jul 2024
- || EVT801 / Kazia
Enrollment closed, Enrollment change, Metastases: Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - Jun 30, 2024
P1, N=32, Active, not recruiting, Sponsor: Kazia Therapeutics Limited
Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Jul 2024 Recruiting --> Active, not recruiting | N=60 --> 32
- | paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Chimerix
Phase classification, Combination therapy: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) - Jun 12, 2024
P2, N=360, Recruiting, Sponsor: University of California, San Francisco
Recruiting --> Active, not recruiting | N=60 --> 32 Phase classification: P1/2 --> P2
- | paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Chimerix
Phase classification, Trial completion date, Combination therapy: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) - Jun 10, 2024
P1/2, N=360, Recruiting, Sponsor: University of California, San Francisco
Phase classification: P1/2 --> P2 Phase classification: P2 --> P1/2 | Trial completion date: Jun 2027 --> Jun 2029
- | paxalisib (GDC-0084) / Kazia, SoVarGen
Trial completion date, Trial primary completion date: Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL (clinicaltrials.gov) - May 20, 2024
P2, N=25, Recruiting, Sponsor: Lakshmi Nayak, MD
Phase classification: P2 --> P1/2 | Trial completion date: Jun 2027 --> Jun 2029 Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: May 2024 --> Dec 2025
- | paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Chimerix
Enrollment open, Enrollment change, Combination therapy: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) - May 9, 2024
P2, N=324, Recruiting, Sponsor: University of California, San Francisco
Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: May 2024 --> Dec 2025 Active, not recruiting --> Recruiting | N=143 --> 324
- ||| SNV1521 / Synnovation Therap
Enrollment open, Metastases: SNV1521-101: SNV1521 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - May 3, 2024
P1, N=76, Recruiting, Sponsor: Synnovation Therapeutics, Inc.
Active, not recruiting --> Recruiting | N=143 --> 324 Not yet recruiting --> Recruiting
- | paxalisib (GDC-0084) / Kazia, SoVarGen
Enrollment closed, Enrollment change: GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases (clinicaltrials.gov) - Mar 27, 2024
P1, N=21, Active, not recruiting, Sponsor: Memorial Sloan Kettering Cancer Center
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting | N=36 --> 21
- | metformin / Generic mfg.
Journal: Just a spoonful of metformin helps the medicine go down. (Pubmed Central) - Mar 19, 2024
To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors.
- | Kinenza (enzastaurin) / Denovo, Aytu BioPharma, paxalisib (GDC-0084) / Kazia
Journal: PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma. (Pubmed Central) - Mar 18, 2024
Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-sequencing, identifying changes in myelination and tumor immune microenvironment crosstalk. Together, we have identified a clinically relevant DIPG therapeutic combinatorial approach.
- || paxalisib (GDC-0084) / Kazia, SoVarGen
Trial completion: Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma (clinicaltrials.gov) - Mar 15, 2024
P2, N=30, Completed, Sponsor: Kazia Therapeutics Limited
Together, we have identified a clinically relevant DIPG therapeutic combinatorial approach. Active, not recruiting --> Completed
- || paxalisib (GDC-0084) / Kazia
Trial completion, Trial completion date: Mass Balance Recovery, Metabolite Profile, and Metabolite Identification of [14C]-Paxalisib in Healthy Male Subjects (clinicaltrials.gov) - Mar 15, 2024
P1, N=6, Completed, Sponsor: Kazia Therapeutics Limited
Active, not recruiting --> Completed Active, not recruiting --> Completed | Trial completion date: Mar 2023 --> Jan 2024
- paxalisib (GDC-0084) / Kazia, SoVarGen
Improving survival of atypical teratoid/rhabdoid tumor orthotopic xenografts through the combination of PI3K inhibitor paxalisib and nucleoside analog gemcitabine (Ballroom 6 A - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_8789;
In CHLA-06 orthotopic tumors combination therapy extended median survival from 22 days for control to 82.5 days (p<0.0001). Based on these findings, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) is planning to include paxalisib/gemcitabine combination therapy in the next international clinical trial for patients with relapsed/recurrent AT/RT.
- EVT801 / Evotec, Kazia
EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, is pursuing dose escalation stage of phase I first-in-human study (Section 49) - Mar 5, 2024 - Abstract #AACR2024AACR_3887;
Based on these findings, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) is planning to include paxalisib/gemcitabine combination therapy in the next international clinical trial for patients with relapsed/recurrent AT/RT. Abstract is embargoed at this time.
- EVT801 / Evotec, Kazia
Biomarkers analysis on samples from patients in EVT801 clinical trial: Patient characterization and immunomonitoring (Section 43) - Mar 5, 2024 - Abstract #AACR2024AACR_2338;
P1
VEGFR3 expression also tends to be correlated with higher levels of hypoxia (CAIX labelling). Our working hypothesis is that patients with hypoxic HGS-OC tumors with high VEGFR3 expression may benefit from EVT801 treatment; this will need to be reinforced by inclusion of additional patients in dedicated PD biomarkers cohorts during stage 2 of the clinical trial.
- | SNV1521 / Synnovation Therap
New P1 trial, Metastases: SNV1521-101: SNV1521 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - Jan 24, 2024
P1, N=76, Not yet recruiting, Sponsor: Synnovation Therapeutics, Inc.
- |||| paxalisib (GDC-0084) / Kazia, SoVarGen, pimasertib (AS703026) / Day One Biopharma
New P1/2 trial: Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer (clinicaltrials.gov) - Jan 17, 2024
P1/2, N=82, Not yet recruiting, Sponsor: Australian & New Zealand Children's Haematology/Oncology Group
- || paxalisib (GDC-0084) / Kazia
PK/PD data, Preclinical, Journal: Preclinical Characterization of the Absorption and Disposition of the Brain Penetrant PI3K/mTOR Inhibitor Paxalisib and Prediction of Its Pharmacokinetics and Efficacy in Human. (Pubmed Central) - Jan 10, 2024
Oral bioavailability ranged from 6% in monkeys to 76% in rats.The parameters estimated from the pharmacokinetic/pharmacodynamic modeling of the efficacy in the subcutaneous U87 xenograft model combined with the human pharmacokinetics profile predicted by PBPK modeling suggested that a dose of 56?mg may be efficacious in humans. Paxalisib is currently tested in Phase III clinical trials.
- | paxalisib (GDC-0084) / Kazia, Tagrisso (osimertinib) / AstraZeneca
Journal: Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma. (Pubmed Central) - Dec 24, 2023
Our results suggest that AZD-9291 combined with GDC-0084 may be considered as a potential treatment strategy in future clinical trials. Video Abstract.
- | paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
Journal: Rational combination platform trial design for children and young adults with Diffuse Midline Glioma: a report from PNOC. (Pubmed Central) - Dec 21, 2023
P2
This combination treatment aimed at inducing metabolic distress led to the design of the first DMG-specific platform trial PNOC022 (NCT05009992). Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such that we offer direction on future clinical trials in DMG.
- |||| Trial completion date, Trial primary completion date: GBM AGILE: A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (clinicaltrials.gov) - Dec 1, 2023
P2/3, N=1030, Recruiting, Sponsor: Global Coalition for Adaptive Research
Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such that we offer direction on future clinical trials in DMG. .
- | paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Chimerix
Enrollment closed, Enrollment change, Combination therapy: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) - Nov 26, 2023
P2, N=143, Active, not recruiting, Sponsor: University of California, San Francisco
. Recruiting --> Active, not recruiting | N=324 --> 143
- paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
PNOC022: A Combination Therapy Trial using an Adaptive Platform Design for patients with Diffuse Midline Gliomas (DMGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression (Room 121-122) - Nov 11, 2023 - Abstract #SNO2023SNO_1506;
The current median OS is encouraging compared to historical controls. At the meeting, we will present updated molecular characterization and early biological correlates in association with clinical outcomes including toxicity, OS, PK, and central imaging confirmed progression-free survival.
- paxalisib (GDC-0084) / Kazia
Phase I study of paxalisib and radiotherapy for CNS disease harboring PI3K pathway mutations: pilot analysis of circulating tumor DNA for patient eligibility confirmation and post-treatment response (Exhibit Hall A/B) - Nov 11, 2023 - Abstract #SNO2023SNO_542;
P1
For patients on genomically-driven targeted therapy and RT combination trials, alterations detected using plasma ctDNA, especially PIK3CA, may be used to rapidly assess eligibility. Serial ctDNA collection may serve as a potential response biomarker with further validation.
- Kinenza (enzastaurin) / Denovo, Aytu BioPharma, paxalisib (GDC-0084) / Kazia
Exploiting the genetic dependency on PI3K/mTOR signaling for the treatment of H3-altered diffuse midline glioma (Room 121-122) - Nov 11, 2023 - Abstract #SNO2023SNO_276;
P1, P2
Mechanisms of adaptation/plasticity were assessed by ATAC-Seq and quantitative proteomic profiling xenograft tumors refractory to treatment. Here we address the intrinsic neoplastic sequela of DIPG, by combined targeting of PI3K/Akt/mTOR using paxalisib, compensatory PKC signaling using enzastaurin, coupled with strategies to manage treatment-related side-effects and reduced efficacy using metformin; providing the preclinical rationale for the addition of metformin to NCT05009992.
- paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
Combining ONC201 and paxalisib for the treatment of diffuse midline glioma (DMG); the preclinical results underpinning the international Phase II clinical trial (NCT05009992). (Exhibit Hall C) - Nov 11, 2023 - Abstract #SNO2023SNO_248;
P2
The patient continuing to receive the combination at progression and following reirradiation also experienced a marked decrease in tumor size (MR axial diagnosis scan = 1248 mm2, current tumour area = 315 mm2, ~75% reduction), 10 months following radiological detection of progression. These data inform the phase II clinical trial (NCT05009992).
- | paxalisib (GDC-0084) / Kazia, SoVarGen
Trial completion date, Trial primary completion date: Paxalisib With a High Fat, Low Carb Diet and Metformin for Glioblastoma (clinicaltrials.gov) - Sep 26, 2023
P2, N=33, Recruiting, Sponsor: Weill Medical College of Cornell University
These data inform the phase II clinical trial (NCT05009992). Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
- EVT801 / Evotec, Kazia
VEGFR-3 expression profiling by histology and mRNA signature to classify patient population for the selective VEGFR-3 inhibitor EVT801 () - Jul 27, 2023 - Abstract #ESMO2023ESMO_1767;
P1
This enables us to select indications that might benefit from EVT801 as a monotherapy (e.g., clear cell renal cell carcinoma and soft tissue sarcomas) or in combination with standard of care. Accordingly, VEGFR-3 expression is retrospectively quantified during the EVT801 phase 1 clinical trial and may be used to stratify patients in the future.
- || paxalisib (GDC-0084) / Kazia
Would love to know when the data for Paxalisib is going to be published? (Twitter) - Jul 25, 2023
- | paxalisib (GDC-0084) / Kazia, SoVarGen
Trial completion date, Trial primary completion date: Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL (clinicaltrials.gov) - Jul 5, 2023
P2, N=25, Recruiting, Sponsor: Lakshmi Nayak, MD
Accordingly, VEGFR-3 expression is retrospectively quantified during the EVT801 phase 1 clinical trial and may be used to stratify patients in the future. Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2024
- | paxalisib (GDC-0084) / Kazia, SoVarGen
Trial completion date, Trial primary completion date: GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases (clinicaltrials.gov) - Jun 5, 2023
P1, N=36, Recruiting, Sponsor: Memorial Sloan Kettering Cancer Center
Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2024 Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
- | paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
Journal, Combination therapy: ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma. (Pubmed Central) - May 17, 2023
P2
Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992. PI3K/Akt signaling promotes metabolic adaptation to ONC201-mediated disruption of mitochondrial energy homeostasis in diffuse intrinsic pontine glioma, highlighting the utility of a combination treatment strategy using ONC201 and the PI3K/Akt inhibitor paxalisib.
- | paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
Journal, Combination therapy: ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma. (Pubmed Central) - May 5, 2023
P2
Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992.
- || paxalisib (GDC-0084) / Kazia, Jyseleca (filgotinib) / Galapagos, Gilead
PK/PD data, Preclinical, Journal: Validated HPLC-UV method for quantification of paxalisib, a pan PI3K and mTOR inhibitor in mouse plasma: Application to a pharmacokinetic study in mice. (Pubmed Central) - Mar 16, 2023
Inter- and intraday precision and accuracy, stability studies, dilution integrity and incurred sample reanalysis were investigated and the results met the acceptance criteria. The validated HPLC method was extended to assess the pharmacokinetic parameters of paxalisib in mice.
- || paxalisib (GDC-0084) / Kazia
Any news on Paxalisib? (Twitter) - Mar 16, 2023
- || paxalisib (GDC-0084) / Kazia
Any update on Paxalisib? (Twitter) - Mar 16, 2023
- paxalisib (GDC-0084) / Kazia
Dual inhibitor of ACVR1 and MEK 1/2 E6201 and PI3K/mTOR inhibitor paxalisib synergistically inhibit cell growth in DMG (Section 17; Poster Board #3) - Mar 14, 2023 - Abstract #AACR2023AACR_7166;
From our data, E6201 as a single agent is a promising therapeutic option for DMG. With further evaluation of combination of E6201 and paxalisib, we believe that combination therapy will be an even more effective treatment option for DMG.
- mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, paxalisib (GDC-0084) / Kazia
The PI3K inhibitor Paxalisib combines synergistically with the MEK inhibitor Mirdametinib to target atypical teratoid/rhabdoid tumors (Section 38; Poster Board #27) - Mar 14, 2023 - Abstract #AACR2023AACR_7091;
With further evaluation of combination of E6201 and paxalisib, we believe that combination therapy will be an even more effective treatment option for DMG. Na
- paxalisib (GDC-0084) / Kazia
Combination of the PI3k inhibitor Paxalisib with the nucleoside analog Gemcitabine over-activates the integrated stress response and induces atypical teratoid/rhabdoid tumor cell death (Section 38; Poster Board #8) - Mar 14, 2023 - Abstract #AACR2023AACR_7073;
Ongoing treatment of mice bearing CHLA06 orthotopic tumors demonstrate that combination therapy further extends median survival. Our studies suggest that pharmacologically activating the ISR may be an effective strategy to target AT/RT and combination of Paxalisib and Gemcitabine may be an effective treatment to help extend survival in this deadly disease.
- Dual inhibition of RAS and the IGF2/IGF1R pathways: a potential targeting strategy for RAS-mutated embryonal rhabdomyosarcoma (Section 44; Poster Board #1) - Mar 14, 2023 - Abstract #AACR2023AACR_4716;
Our studies suggest that pharmacologically activating the ISR may be an effective strategy to target AT/RT and combination of Paxalisib and Gemcitabine may be an effective treatment to help extend survival in this deadly disease. Combination of comprehensive genomic profiling and a laboratory-based 3D micro-cancer model using the patient
- paxalisib (GDC-0084) / Kazia
Newer generation mTOR inhibition represents effective therapeutic strategy for BRAF-mutant melanoma (Section 15; Poster Board #22) - Mar 14, 2023 - Abstract #AACR2023AACR_2523;
The dual PI3K/mTORC inhibitor, Paxalisib, significantly reduced cell proliferation greater than combination AKT/SGK inhibition and resulted in increased overall survival in a BRAF-driven immunocompetent mouse model of melanoma (p=0.0003 vs vehicle). These results allow insight into compensatory signaling networks upon AKT inhibition and suggest that dual targeting of PI3K and both mTOR complexes may represent an effective and tolerable therapeutic strategy in this disease that could further be combined with standard of care targeted therapy.