CoChat
Sign Up
Cited by 23Cancer Immunotherapy and BiomarkersCancer-related Molecular PathwaysCutaneous Melanoma Detection and Management

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs.

Tolcher, Anthony W., Reeves, James Andrew, McKean, Meredith, Chmielowski, Bartosz, Beck, Joseph Thaddeus, Shaheen, Montaser F., Somaiah, Neeta, Wilson, Melissa +10 more·2021·Journal of Clinical Oncology
DOI 10.1200/jco.2021.39.15_suppl.2506
Open this paper in CoChat — free account

Abstract

2506 Background: Alrizomadlin (APG-115) restores TP53 function, activating p53-mediated apoptosis in tumor cells with wild-type TP53 and/or MDM2 amplification. Alrizomadlin also functions as a host immunomodulator and hence may restore antitumor activity in pts with cancers failing PD-1/PD-L1 blockade. Methods: This US multicenter trial assessed alrizomadlin combined with pembrolizumab in pts with unresectable/metastatic melanoma or advanced solid tumors that had failed I-O drugs; or pts with malignant peripheral nerve sheath tumor (MPNST), liposarcoma, or ATM mutant solid tumors that had failed any standard therapy. Eligible pts had ECOG performance status of 0-2 and no CNS metastases. The phase II study cohorts included pts with melanoma, NSCLC, solid tumor with ATM mutation, well-differentiated/dedifferentiated liposarcoma, urothelial carcinoma, and MPNST. Alrizomadlin was administered orally at 150 mg once every other day for 2 consecutive weeks with 1 week off and pembrolizumab at 200 mg via IV infusion for 30 minutes on Day 1 of a 21-day cycle. Results: As of December 25, 2020, 84 pts had been treated in 6 cohorts: melanoma (n = 26), NSCLC (n = 23), ATM mutation (n = 9), liposarcoma (n = 14), urothelial (n = 9), and MPNST (n = 3). In the PD-1/PD-L1 inhibitor-failed melanoma cohort, there was 1 confirmed partial response (PR) out of 5 pts with uveal melanoma, 2 PR (1 confirmed and 1 unconfirmed) of 5 pts with mucosal melanoma, and 1 confirmed PR of 11 pts with cutaneous melanoma. ORR in the melanoma cohort was 17.4% (4/23 evaluable pts), and the disease control rate was 60.9% (14/23). In the MPNST cohort, 1 of 3 pts had an unconfirmed ongoing PR. In I-O drug-failed NSCLC (n = 14 evaluable) and urothelial (n = 5 evaluable) cohorts, each reported 1 confirmed PR. Common treatment (alrizomadlin or pembrolizumab)-related adverse events (TRAEs) (≥ 10%) were nausea (63.1%), thrombocytopenia (36.9%), vomiting (33.3%), fatigue (31.0%), decreased appetite (27.4%), diarrhea (21.4%), neutropenia (15.4%), and anemia (11.9%). Grade ≥ 3 TRAEs (≥ 5%) included thrombocytopenia (20.2%), neutropenia (14.2%), and anemia (8.3%). Eleven pts discontinued treatment due to AEs: 5 were treatment related, including 2 grade 4 thrombocytopenia, and 1 each of grade 2 vomiting, grade 2 fatigue, and grade 2 posterior reversible encephalopathy syndrome (PRES). Three treatment-related SAEs were PRES, pyrexia, and asthenia. Conclusions: Alrizomadlin combined with pembrolizumab is well tolerated and may restore antitumor effects in pts with cancer resistant to or intolerant of I-O drugs, as suggested by preliminary antitumor activities in multiple tumor types. Internal study identifiers: APG-115-US-002; Keynote MK-3475-B66. Clinical trial information: NCT03611868.

Integrity signals

Registry

Crossref · 10.1200/jco.2021.39.15_suppl.2506

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Still being checked.

Cited by

Sorted by citations

Related

Authors
Tolcher, A. W., Reeves, J. A., McKean, M., Chmielowski, B., Beck, J. T., Shaheen, M. F., Somaiah, N., Wilson, M., Spira, A. I., Drabick, J. J., Tang, Y., Winkler, R., Li, M., Ahmad, M., Lu, M., Liang, Z., Yang, D., & Zhai, Y.
Affiliations
  • Texas Oncology-San Antonio Babcock, San Antonio, TX;
  • Florida Cancer Specialists South/Sarah Cannon Research Institute, Fort Myers, FL;
  • Tennessee Oncology (US)
  • University of California, Los Angeles (US)
  • Highlands Oncology Group (US)
  • University of Arizona Cancer Center (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • Thomas Jefferson University (US)
  • Virginia Cancer Specialists (US)
  • Pennsylvania State University (US)
  • Ascentage Pharma Group Inc. (United States) (US)
  • Sun Yat-sen University (CN)
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2021-05-20
Volume
39
Issue
15_suppl
Pages
2506-2506
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2021.39.15_suppl.2506
OpenAlex
W3170127104
Cited by
23
References
0
Citations by year
2026: 3 · 2025: 1 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 1
Type
conference abstract
Language
en
Open access
closed
Locations
Journal of Clinical Oncology (publishedVersion)
Funders
Ascentage Pharma Group Corp Ltd
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords
MDM2 inhibitors, pembrolizumab, melanoma, metastatic melanoma, PD-1/PD-L1 inhibitor resistance, combination immunotherapy, ATM mutations, liposarcoma, urothelial carcinoma, malignant peripheral nerve sheath tumor, non-small cell lung cancer, oral small-molecule therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review