Reference Detail

Ref Type

Abstract

PMID

Authors

Noboru Yamamoto, Navid Hafez, Anthony W. Tolcher, Michael Teufel, Junxian Geng, Liz Svensson, Mehdi Lahmar, Mrinal M. Gounder

Title

A phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 (ezabenlimab) and BI 754111 in patients (pts) with advanced solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	40	16_suppl	June 1, 2022

URL

https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.3095

Abstract Text

3095. Background: Preclinical data show that combining a murine double minute 2–tumor protein 53 (MDM2–p53) antagonist with immune checkpoint inhibitors produces anti-tumor effects in multiple tumor types. This Phase Ia/Ib study (NCT03964233) is assessing BI 907828, a MDM2–p53 antagonist, combined with immune checkpoint inhibitors in TP53 wild-type cancers. Methods: In Phase Ia (dose escalation), pts with advanced/metastatic solid tumors received escalating doses of BI 907828 guided by a Bayesian Logistic Regression Model (starting dose 10 mg orally) plus ezabenlimab 240 mg (anti-PD-1 antibody) and BI 754111 600 mg (anti-LAG-3 antibody) every 21 days (q3w). Primary endpoint was the maximum tolerated dose (MTD) of BI 907828 based on the number of pts with dose-limiting toxicities (DLTs) during cycle one. During Phase Ia, other studies indicated a lack of added efficacy when BI 754111 was combined with ezabenlimab; therefore, the study design was updated to switch the dose escalation to the doublet combination of BI 907828 plus ezabenlimab. Results: A total of 11 pts received the triplet combination at 10/20/30/45 mg dose levels (DL; n = 3/3/3/2 respectively); all have discontinued treatment. No DLTs were reported in cycle one; MTD was not reached. As of 20th January 2022, 15 pts have received the doublet combination at 30/45 mg DLs (n = 10/5 respectively). One pt (45 mg) had a DLT during cycle one: G2 neutropenia. Four DLTs were reported after cycle one: G3 anemia (30 mg); G2 thrombocytopenia (45 mg); and G3 neutropenia and G4 thrombocytopenia (45 mg). G≥3 adverse events occurred in eight pts; most commonly anemia (n = 6), thrombocytopenia (n = 4) and lymphopenia (n = 3). There were no notable safety findings with BI 907828 45 mg q3w, the recommended dose for expansion (RDE) for BI 907828 monotherapy. Nine of the 15 pts who received doublet therapy were evaluable for response; four had a confirmed partial response (PR; 30 mg, n = 1; 45 mg, n = 3), two biliary tract carcinoma, one urothelial carcinoma, and one myxoid liposarcoma; one had an unconfirmed PR (30 mg) with adenocarcinoma (primary site intrahepatic cholangiocarcinoma). Four pts with liposarcoma and gastric cancer had stable disease. MTD will be reported. In Phase Ib, pts will receive the RDE of BI 907828 plus 240 mg ezabenlimab (q3w). Pts will be recruited to two cohorts: soft tissue sarcomas (liposarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, synovial sarcoma and leiomyosarcoma) and selected MDM2-amplified tumors (NSCLC, gastric adenocarcinoma, urothelial carcinoma, and biliary tract carcinoma). Primary endpoints are progression-free survival and objective response (RECIST 1.1). Conclusions: The doublet combination of BI 907828 plus ezabenlimab showed a manageable safety profile and early signs of anti-tumor activity. Eleven pts remain on treatment; recruitment is ongoing. Clinical trial information: NCT03964233.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
TP53 wild-type	Advanced Solid Tumor	predicted - sensitive	BI 907828 + Ezabenlimab	Phase I	Actionable	In a Phase I trial, Ezabenlimab (BI 754091) and BI 907828 combination therapy demonstrated safety in patients with TP53 wild-type advanced solid tumors (n=9), and resulted in a partial response (PR) in 2 patients with biliary tract carcinoma, 1 urothelial carcinoma patient, and 1 myxoid liposarcoma patient, an unconfirmed PR in an intrahepatic cholangiocarcinoma patient, and stable disease in 4 patients with liposarcoma or gastric cancer (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3095; NCT03964233).	detail...