Evidence map›Paper›PMID 41231232›Full record

Trial reportCancer research communications2025

BrUOG360: A Phase Ib/II Study of Copanlisib in Combination with Rucaparib in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Andre L De Souza, Matthew J Hadfield, Shaolei Lu, Dragan J Golijanin, Roxanne Wood, Jeannine Margolis, Kate Anderson, Adam J Olszewski, Sheldon L Holder, Wafik S El-Deiry and 3 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. 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

13 authors.

Andre L De Souza *Legorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0009-0008-1831-1719
Matthew J Hadfield *Legorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0000-0001-5824-1286
Shaolei LuDepartment of Pathology, Brown University, Providence, Rhode Island.ORCID 0000-0003-2870-5793
Dragan J GolijaninLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0009-0004-4477-2173
Roxanne WoodLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0009-0007-3623-4959
Jeannine MargolisLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0009-0002-5747-4939
Kate AndersonBrown University Health Cancer Institute, East Greenwich, Rhode Island.ORCID 0009-0007-1561-7766
Adam J OlszewskiLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0000-0002-6472-6658
Sheldon L HolderLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0000-0002-8959-2879
Wafik S El-DeiryLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0000-0002-9577-8266
Rahul R AggarwalHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.ORCID 0000-0001-7003-7982
Anthony E MegaLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0009-0008-6409-9325
Benedito A CarneiroLegorreta Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, Rhode Island.ORCID 0000-0002-5468-1126

Funding

Bayer (Bayer AG)Clovis Oncology
6 · The paper itself

Abstract

purposeMetastatic castration-resistant prostate cancer with homologous recombination (HR) deficiency (HRD) is sensitive to PARP inhibitors (PARPi). PI3K inhibitors (PI3Ki) sensitize to PARPi by disrupting HR in preclinical models. This phase Ib/II study investigated copanlisib (Copa; pan-class I PI3Ki) and rucaparib (R). PATIENTS AND

methodsEligible patients had metastatic castration-resistant prostate cancer treated with ≥1 androgen receptor inhibitor and taxanes. Phase I followed a standard 3 + 3 dose-escalation design (rucaparib 400-600 mg orally twice a day; Copa 45-60 mg i.v. on days 1, 8, and 15). Primary goal of phase I was to establish MTD and the recommended phase II dose. The primary endpoint of phase II was PSA50 response rate.

resultsThirteen patients enrolled had a median age of 64 (55-78) years and PSA was 11.7 ng/mL (0.018-2,101). Seven patients received taxanes, and one patient received PARPi. Eight patients had HRD+ tumors [BRCA2 (four), BRCA1 (one), RAD51C (one), CDK12 (one), and FANCA (one)] and three had PTEN loss. There were two dose-limiting toxicities in dose level 1 (rucaparib 400 mg twice a day; Copa 45 mg on days 1, 8, and 15): grade 3 rash and aspartate aminotransferase/alanine aminotransferase elevation. Treatment-related adverse events ≥ grade 2 included leukopenia (54%), anemia (38%), rash (30%), fatigue (23%), and neutropenia (23%). Six patients were treated at dose level -1 without dose-limiting toxicities, which was established as the recommended phase II dose (rucaparib 400 mg twice a day + Copa 45 mg on day 1/15). Among patients with HRD+, one had confirmed partial response and three had stable disease by RECIST, including one patient treated with prior PARPi, and three patients had PSA50 responses (23%).

conclusionsCopa/R had an acceptable safety profile with a signal of efficacy supporting future studies of PARPi with PI3Ki. SIGNIFICANCE: Gene alterations in the PI3K and HR pathways are common in prostate cancer. Based on preclinical studies, the inhibition of PI3K disrupts HR, and PARP blockade induces AKT activation, supporting the combination of PI3Ki and PARPi. Herein, we investigated the safety and preliminary efficacy of the PI3Ki copanlisib and the PARPi rucaparib in patients with or without alterations in HR repair pathway genes.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsIndolesProstatic Neoplasms, Castration-ResistantQuinazolinesAgedHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm MetastasisPoly(ADP-ribose) Polymerase InhibitorsProstate-Specific AntigenPyrimidinescopanlisibIndolesPoly(ADP-ribose) Polymerase InhibitorsProstate-Specific AntigenPyrimidinesQuinazolinesrucaparib

Identifiers

PMID41231232
PMCPMC12690636

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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.