Evidence map›Paper›PMID 40471518›Full record

Trial reportBreast cancer research and treatment2025

Phase I/II trial investigating gedatolisib plus talazoparib in advanced triple negative or BRCA1/2 positive, HER2 negative breast cancers.

Sneha Phadke, Kathy D Miller, Ami Shah, Oana C Danciu, Yi Chen, Menggang Yu, Mark E Burkard, Kari B Wisinski

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03911973 (Phase 2 Trial With Safety Run-In of Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers Big Ten Cancer Research Consortium BTCRC-BRE18-337), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03911973 phase1 / phase2active not recruitingnot on this map

Phase 2 Trial With Safety Run-In of Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers Big Ten Cancer Research Consortium BTCRC-BRE18-337

TypeinterventionalSponsorKari WisinskiRan2019 to 2024Enrolled37ConditionsTNBC - Triple-Negative Breast CancerArmsGedatolisib, Talazoparib
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Sneha PhadkeCarver College of Medicine Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, C21GH, Iowa City, IA, 52242, USA. Sneha-Phadke@uiowa.edu.ORCID http://orcid.org/0000-0002-9829-1066
Kathy D MillerMelvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, IN, USA.
Ami ShahRobert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
Oana C DanciuUniversity of Illinois Cancer Center, Chicago, IL, USA.
Yi ChenDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
Menggang YuDepartment of Biostatistics, University of Michigan - Ann Arbor, Ann Arbor, MI, USA.
Mark E BurkardCarver College of Medicine Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, C21GH, Iowa City, IA, 52242, USA.
Kari B WisinskiCarbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeMetastatic triple negative breast cancer has a poor prognosis with limited targeted treatment options. In preclinical studies PI3K inhibition led to increased DNA damage and subsequent sensitization to PARP inhibition. This study aimed to investigate the safety and efficacy of the combination of an mTOR/pan-PI3K inhibitor, gedatolisib, with the PARP inhibitor, talazoparib, in patients with advanced triple negative breast cancer or advanced HER2 negative breast cancer and a germline BRCA1/2 mutation.

methodsThe primary objective of the safety run-in was safety and tolerability of the combination and for dose escalation to find the maximum tolerated dose. A 3 + 3 design was utilized for dose escalation. The primary objective of the phase II study was objective response rate (ORR) in the patients with wildtype germline BRCA1/2. The prespecified efficacy threshold was 20%. Secondary objectives included progression-free (PFS) and overall survival (OS) as well as correlative testing, examining homologous recombination deficiency (HRD) status.

resultsThe combination of gedatolisib and talazoparib carried manageable toxicities with a low incidence of grade 3 adverse events. The most common adverse events of all grades were anemia, fatigue, and oral mucositis. The ORR in the phase II study was 12%. There were no new safety signals identified in the phase II study. mPFS was 2.5 months (95% CI 1.71, 9.89), and mOS was 7 months (95% CI 4.3, NA) in the full phase II cohort. HRD status was analyzed by high (≥ 33) or low (< 33) genomic instability score, and there was no difference in response rate between the groups.

conclusionThe combination of gedatolisib and talazoparib is safe but did not meet the prespecified efficacy threshold for objective response rate. Additional preclinical studies of these pathways are warranted prior to future clinical trials of the combination.

trial registrationClinicalTrials.gov ID: NCT03911973, Date of registration: 2019-04-11.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsPhthalazinesTriple Negative Breast NeoplasmsAdultAgedBRCA1 ProteinBRCA2 ProteinErb-b2 Receptor Tyrosine KinasesFemaleGerm-Line MutationHumansMiddle AgedPoly(ADP-ribose) Polymerase InhibitorsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPhthalazinesPoly(ADP-ribose) Polymerase InhibitorstalazoparibHomologous repair deficiencyMTOR/PI3 K inhibitorPARP inhibitorTriple negative breast cancer

Identifiers

PMID40471518
PMCPMC12208992

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.