Truqap (capivasertib) / Otsuka, AstraZeneca - LARVOL DELTA

Enhanced Efficacy and Differences in Downstream Pathway Modulation with AKT Degradation vs Inhibition in Myeloma. (IMS 2026) - " We designed novel PROTACs based on the AKT inhibitor capivasertib (capi, FDA approved for a subset of metastatic breast cancer), an appropriate linker and a phenyl glutarimide (PG) cereblon binding component... AKT degradation with CCT410766 was associated with a greater effect on cell viability and evidence of cytotoxicity compared to cytostasis seen with AKT inhibition. This enhanced efficacy and the differences in downstream signalling pathway changes may enable greater therapeutic potential for MM than that seen with AKT inhibitors."

Clinical • Breast Cancer • Hematological Malignancies • Multiple Myeloma • Solid Tumor • Targeted Protein Degradation • AKT1 • AKT2 • CRBN • IKZF1

A Phase I Study of Capivasertib in Combination With Abiraterone Acetate in Patients With Metastatic Castration-Resistant Prostate Cancer. (PubMed, Clin Genitourin Cancer) - "The combination of capivasertib and abiraterone acetate had an acceptable tolerability profile consistent with the known profile of each agent. These data support further evaluation of capivasertib and abiraterone acetate in patients with advanced prostate cancer."

Combination therapy • Journal • Metastases • P1 data • Acute Kidney Injury • Diabetes • Genito-urinary Cancer • Hematological Disorders • Nephrology • Oncology • Pain • Prostate Cancer • Renal Disease • Solid Tumor • AR

Capivasertib (C) and fulvestrant (F) for patients (pts) with HR+/HER2- advanced breast cancer (ABC): Final overall survival (OS) results from the phase III CAPItello-291 trial (ESMO-BC 2026) - P3 | "Although OS was not significantly improved, C + F prolonged PFS2 and TFSC for the PIK3CA/AKT1/PTEN-altered and overall populations, indicating clinically meaningful benefit vs pbo + F. Safety was consistent with the primary analysis."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • CDK4 • HER-2 • PIK3CA • PTEN

Durvalumab Plus Paclitaxel, with or without Capivasertib or Oleclumab, in Patients with Locally Advanced/Metastatic Triple-Negative Breast Cancer. (PubMed, Clin Cancer Res) - P1/2 | "These findings support the clinical activity and tolerability of durvalumab plus paclitaxel in locally advanced unresectable/mTNBC, as expected for an immune checkpoint inhibitor in combination with chemotherapy. Addition of capivasertib or oleclumab to this treatment combination showed no substantial additional benefit. PD-L1 expression was associated with enhanced antitumor activity across all arms."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1 • PIK3CA • PTEN

AKT inhibition with capivasertib in breast cancer: Clinical evidence, biomarker selection and resistance patterns. (ESMO 2026) - No abstract available

Biomarker • Clinical • Breast Cancer • Oncology • Solid Tumor

Capivasertib and fulvestrant for patients with HR-positive/HER2-negative advanced breast cancer: analysis of the subgroup of patients from Japan in the phase 3 CAPItello-291 trial. (PubMed, Breast Cancer) - "Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen."

Journal • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

DESTINY-Breast08: a phase 1b study of trastuzumab deruxtecan in combination with other anticancer therapies in patients with HER2-low metastatic breast cancer. (PubMed, Clin Cancer Res) - "Safety results were generally consistent with known individual profiles for T-DXd and combination drugs. T-DXd plus capecitabine, capivasertib, anastrozole, or fulvestrant demonstrated preliminary clinical activity in patients with HER2-low mBC."

Journal • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. (PubMed, N Engl J Med) - P3 | "Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.)."

Clinical • Journal • Metastases • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

Patient reported outcomes (PRO) and tolerability of capivasertib (capi) plus abiraterone (abi) versus placebo (pbo) plus abi in patients (pts) with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281. (ASCO-GU 2026) - P3 | "Common capi-associated AEs occur early and are clinically manageable. While pts in the capi+abi arm had more symptomatic AEs (eg diarrhea, rash) consistent with faster decline in self-reported PWB compared with pts in the pbo+abi arm, this did not affect other functional aspects of life (eg work, sleep) and overall HRQoL, allowing for continued treatment with capi+abi."

Clinical • Metastases • Patient reported outcomes • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PTEN

Patient-reported outcomes from the Phase 3 CAPItello-291 trial investigating capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR-positive/HER2-negative advanced breast cancer (SABCS 2023) - P3 | "Pts treated with C-F maintained HRQoL for longer than pts treated with P-F on all EORTC QLQ-C30 functional and symptom domain scores, except diarrhea. Worsening of diarrhea was observed with C-F, consistent with the safety profile of C, but events appeared tolerable and did not negatively impact GHS/HRQoL. Together with the clinical efficacy and manageable safety profile of C-F, the PRO results from the CAPItello-291 trial further support a positive benefit–risk profile of the combination in this population."

Clinical • Metastases • P3 data • Patient reported outcomes • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR positive/HER2-negative advanced breast cancer: exploratory analysis of PFS by AKT pathway gene from the Phase 3 CAPItello-291 trial (SABCS 2023) - P3 | "Compared with fulvestrant alone, the addition of capivasertib to fulvestrant provided a consistent PFS benefit across alterations in all three key genes within the AKT pathway in patients with HR-positive/HER2-negative ABC."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2 • PIK3CA • PTEN

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. (PubMed, Lancet Oncol) - P1b/2 | "Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer. The expanded biomarker testing suggested that capivasertib predominantly benefits patients with PI3K/AKT/PTEN pathway-altered tumours. Phase 3 data are needed to substantiate the results, including in patients with previous CDK4/6 inhibitor exposure who were not included in the FAKTION trial."

Biomarker • Journal • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Infectious Disease • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ER • HER-2 • PIK3CA

A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/PIK3CA-mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2). (ASCO 2026) - P3 | "Geda has superior preclinical potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus and demonstrated activity in PIK3CA-MT and wild-type (WT) breast cancer cell lines. These data demonstrate that gedatolisib combination therapies offer a potential new standard of care as 2L treatment of HR+/HER2- ABC, irrespective of PIK3CA mutation status."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

A phase III study of capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281 (ESMO 2025) - P3 | "The safety profile was broadly consistent with the known profiles of capi and abi. Capi in combination with abi represents a potential first-in-class targeted treatment for this poor prognosis population with high unmet need."

Clinical • Metastases • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PTEN

Capivasertib plus fulvestrant in hormone receptor-positive (HR+) advanced breast cancer (ABC): exploratory ctDNA analyses from the Phase 3 CAPItello-291 trial (SABCS 2025) - "ctDNA analysis offers a minimally invasive option to identify PIK3CA/AKT1/PTEN alterations in HR+ ABC, particularly for pts without suitable tumor tissue analysis. However, ctDNA testing alone may miss alterations, such as in cases of low ctDNA shedding (TF <0.1%), warranting a confirmatory tissue test. The PFS benefit of C + F vs pbo + F in the ctDNA-altered group was consistent with the primary tissue-based analysis."

Circulating tumor DNA • Metastases • P3 data • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • CDK4 • HER-2 • PIK3CA • PTEN

Capivasertib (C) + paclitaxel (P) as first-line treatment of metastatic triple-negative breast cancer (mTNBC): The CAPItello-290 phase III trial (ESMO 2024) - P3 | "First-line C+P for mTNBC did not meet the predefined threshold for improving OS vs Pbo+P in either the overall population or in pts with PIK3CA/AKT1/PTEN-altered tumours. PFS numerically favoured C+P vs Pbo+P. The safety profile of C+P was broadly consistent with the known profiles of C and P."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1 • PIK3CA • PTEN

Comprehensive Molecular and Genomic Analysis of NCI-MATCH Subprotocol Y: Capivasertib in Patients With an AKT1 E17K-Mutated Tumor. (PubMed, JCO Precis Oncol) - "In patients with AKT1 E17K-mutated tumors, capivasertib achieved a clinically significant ORR. TP53 mutations appear to be associated with response, whereas certain additional PI3K/AKT/mTOR pathway mutations and EGFR overexpression appear to be associated with nonresponse to capivasertib. Further investigation of predictive biomarkers is warranted."

Journal • Oncology • AKT1 • EGFR • TP53

Capivasertib + fulvestrant for patients (pts) with hormone receptor-positive (HR+) advanced breast cancer (ABC): Management of common adverse events (AEs) from the Phase III CAPItello-291 trial (ESMO 2026) - No abstract available

Adverse events • Clinical • Metastases • P3 data • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Capivasertib plus fulvestrant in PIK3CA/AKT/PTEN-altered HR+/HER2- advanced breast cancer: a multicentre real-world study (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial. (PubMed, Eur J Cancer) - "Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC."

Combination therapy • Journal • Metastases • P2 data • Fatigue • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PTEN

Capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN-deficient metastatic hormone sensitive prostate cancer (mHSPC): updated overall survival (OS) from CAPItello-281 (ESMO 2026) - No abstract available

Clinical • Late-breaking abstract • Metastases • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • PTEN

Targeted therapy for DNA damage response and homologous recombination repair defects: The Olaparib Combinations trial. (PubMed, Cancer) - "The study failed to meet its primary end point of ORR. DDR and homologous recombination repair defects are not consistently actionable with olaparib as monotherapy or in combination with other targeted therapies in a histology-agnostic manner."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • HRD

Triplet Therapy Options for Metastatic Hormone-Sensitive Prostate Cancer - Alicia Morgans & Sandy Srinivas (UroToday) - "Alicia Morgans...discuss selecting triplet therapy in metastatic hormone-sensitive prostate cancer. Dr. Morgans favors docetaxel triplets for de novo, high-volume disease, particularly with visceral involvement or cord compression...Dr. Morgans also favors capivasertib plus abiraterone over docetaxel in patients with PTEN loss, reserving docetaxel for later."

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capivasertib (Truqap) is accepted for restricted use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative (defined as IHC 0 or 1+, or IHC 2+/ISH-) locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following recurrence or progression on or after an endocrine based regimen. SMC restriction: restricted to patients whose disease has progressed following CDK4/6 inhibitor plus aromatase inhibitor therapy. Evidence from a double-blind, phase III study, demonstrated that addition of capivasertib to fulvestrant significantly improved progression-free survival (PFS) but not overall survival (OS)."

Reimbursement • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study (SABCS 2025) - " ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms...PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance... Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Table 1:Phase 2 mPFS, mo[95% CI] in all patients and subgroupsNR, not reached"

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA