Evidence map›Paper›PMID 39998620›Full record

ArticleCancer chemotherapy and pharmacology2025

A phase 1 study of the combination of BH3-mimetic, navitoclax, and mTORC1/2 inhibitor, vistusertib, in patients with advanced solid tumors.

Susan C Scott, Anna Farago, W Victoria Lai, Marianna Zahurak, Michelle A Rudek, Judy Murray, Michael A Carducci, Tamar Uziel, Naoko Takebe, Steven D Gore and 2 more

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

Article in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03366103 (Phase 1/2 Study of Navitoclax Plus Vistusertib in Patients With Relapsed Small Cell Lung Cancer), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

NCT03366103 phase1 / phase2terminatednot on this map

Phase 1/2 Study of Navitoclax Plus Vistusertib in Patients With Relapsed Small Cell Lung Cancer (SCLC) and Other Solid Tumors

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2018 to 2022Enrolled15ConditionsMetastatic Malignant Solid Neoplasm, Recurrent Lung Small Cell Carcinoma, Recurrent Malignant Solid Neoplasm, Refractory Malignant Solid NeoplasmArmsNavitoclax, Vistusertib
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026
    Review
  3. 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

12 authors.

Susan C ScottDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Anna FaragoKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
W Victoria LaiDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Marianna ZahurakDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Michelle A Rudek *Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Judy MurrayDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Michael A CarducciDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Tamar UzielOncology Discovery, AbbVie Inc, North Chicago, IL, USA.
Naoko TakebeIDB/CTEP/NCI, National Cancer Institute, Rockville, MD, USA.
Steven D GoreIDB/CTEP/NCI, National Cancer Institute, Rockville, MD, USA.
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Christine L HannDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. chann1@jhmi.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
XPO1 inhibitors Selinexor and Eltanexor in Combination with Venetoclax and Decitabine (ASTX727) in AMLUM1CA186709 · NCI · DANA-FARBER CANCER INST · PI KEITH T FLAHERTY, DONALD W. KUFE · 2014 to 2026
$25.9M
The Johns Hopkins Translational Science Team for the ET-CTNUM1CA186691 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Michael A Carducci · 2014 to 2026
$21.9M
Novel therapeutic development for small cell lung cancerR35CA263816 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Charles M. Rudin · 2021 to 2026
$6.3M
The Chesapeake-Ohio Pharmacokinetics Core for The ETCTNU24CA247648 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Mitch A Phelps · 2020 to 2026
$3.6M
NCI NIH HHS 1UM1CA186709-01NCI NIH HHS 2UM1CA186691-06NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA008748NCI NIH HHS R35 CA263816NCI NIH HHS U24 CA247648NCI NIH HHS UM1 CA186691NCI NIH HHS UM1 CA186709
6 · The paper itself

Abstract

purposeTo determine the, safety, tolerability and recommended phase 2 dosing of the combination of navitoclax, a dual Bcl-2/xL inhibitor, and vistusertib, a TORC1/2 inhibitor.

methodsPatients with advanced solid tumors received navitoclax plus vistusertib following a 3 + 3 dose escalation design. To mitigate thrombocytopenia, a known toxicity of navitoclax, all patients received lead-in dosing of navitoclax alone at 150 mg orally daily for a minimum of 7 days. In addition to safety and tolerability, pharmacokinetics of navitoclax and vistusertib were evaluated.

results14 patients received combination treatment which was well-tolerated at dose level 1 (navitoclax 150 mg orally daily plus vistusertib 35 mg orally twice daily). The main dose-limiting toxicity, grade 3 serum aminotransferase elevation, occurred in two of five patients at dose level 2 (navitoclax 250 mg orally daily plus vistusertib 35 mg orally twice daily). Navitoclax and vistusertib exposures appeared consistent with levels reported in prior studies of each agent. No responses were observed among the 8 response evaluable patients.

conclusionsA tolerable dose of navitoclax at 150 mg orally daily plus vistusertib at 35 mg orally twice daily was identified in patients with advanced solid tumors and established as the recommended phase 2 dose (RP2D). Further efficacy assessment of this combination, in a planned phase 2 expansion in patients with relapsed small cell lung cancer, was terminated due to discontinuation of vistusertib.

trial registrationNCT03366103 (First posted December 8, 2017).

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsNeoplasmsAdultAgedAniline CompoundsBenzamidesDose-Response Relationship, DrugFemaleHumansIndolesMaleMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Middle AgedMorpholinesPyrimidinesAniline CompoundsBenzamidesIndolesMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MorpholinesnavitoclaxPyrimidinesSulfonamidesvistusertib

Identifiers

PMID39998620
PMCPMC12235654

What Socratic holds

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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 Socratic graph.