Reference Detail

Ref Type

Abstract

PMID

Authors

Chrisann Kyi, Marloes Van Dongen, Sylvie Rottey, Ignacio Melero Bermejo, Diana Mittag, Dane Gouveia, Kees Bol, Chris Yan, Andrew K. Joe, Gianluca Laus, and Victor Moreno

Title

Phase I study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1, in solid tumors, as monotherapy or in combination with pembrolizumab.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	42	no. 16_suppl	May 29, 2024	2520	J Clin Oncol

URL

https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2520

Abstract Text

Background: MCLA-145, a human common light chain bispecific antibody targeting CD137 and the PD-1/PD-L1 axis, is designed to enhance both antigen-mediated T cell activation via CD137 costimulation, and blockade of inhibitory PD-L1. Interim data from the ongoing phase 1 study (NCT03922204) are presented. Methods: Patients (pts) with PD-L1 ≥1% advanced/metastatic solid tumors received MCLA-145 IV as monotherapy Q2W/Q3W in 21/28-d cycles respectively, or in combination with pembrolizumab 200 mg Q3W in 21-d cycles. Pts enrolled in combination had cancers that either relapsed after PD-(L)1 therapies or were immunotherapy naïve. Primary objectives are safety, tolerability and dose-limiting toxicity (DLT) of MCLA-145 alone or combined with pembrolizumab, and determination of the recommended dose for expansion (RDE). Secondary endpoints include efficacy, pharmacokinetics, pharmacodynamics (PD) and immunogenicity. Results: As of a December 4, 2023 data cutoff, 72 pts with 26 cancer types were treated; 25% of pts had non-small cell lung cancer (NSCLC). 3 pts were continuing combination therapy. Monotherapy: 53 pts (median age 60 y, 49% male) were treated across 8 dose levels (47 pts 0.4-75 mg Q2W, 6 pts 40 mg Q3W). Median number of cycles was 2 (range 1-39). 6 pts had DLTs in the 25-75 mg dose range (febrile neutropenia [2 pts], hemolytic anemia, myositis, ALT/AST increase, neutrophil/platelet decrease [1 pt each]). Most common adverse events (AEs; all grades/G3-4) were fatigue (51%/4%), decreased appetite (34%/2%), dyspnea (32%/0%), anemia (30%/9%), ALT/AST increase (25%/11%), and pyrexia (25%/0%). The incidence of any G3-4 AE was lower with 40 mg Q3W than across all Q2W dose levels (33% vs 66%). Combination: 19 pts (median age 61 y, 47% male) were treated with MCLA-145 10, 25 or 40 mg plus Q3W. Median number of cycles was 5 (range 1-16). No DLTs occurred. Most common AEs (all grades/G3-4) were fatigue (58%/11%), cough (42%/0%), constipation (32%/0%) and ALT/AST increase (21%/11%). The RDE was established at 40 mg Q3W for both monotherapy and combination. Preliminary antitumor activity was observed with monotherapy (52 evaluable pts): 5 partial responses (PRs) in glioblastoma (lasting >3 y), sarcoma, cervical, anal, and gastric cancer (treated for 2-11 mo); and combination (19 evaluable pts): 1 PR in Merkel cell carcinoma (treated 12+ mo), 1 complete response in PD-L1+ NSCLC (treated 6+ mo), both after prior immunotherapy. Disease control rate was 37% with monotherapy and 68% with combination. Exposure was dose-dependent with a terminal half-life of 69 h at 75 mg. Measure of peripheral blood Ki67+ CD8 T cells supports maximal PD activity at 40 mg. Conclusions: MCLA-145 given alone or in combination with pembrolizumab had a well-tolerated and manageable safety profile with encouraging clinical activity, including in pts who relapsed after PD-(L)1 therapies. Clinical trial information: NCT03922204.

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
CD274 positive	Advanced Solid Tumor	predicted - sensitive	MCLA-145 + Pembrolizumab	Phase I	Actionable	In a Phase I trial, treatment with the combination of MCLA-145 and Keytruda (pembrolizumab) demonstrated safety and activity in patients with CD274 (PD-L1)-positive advanced solid tumors (n=19), resulting in 1 complete response in a patient with non-small cell lung cancer and 1 partial response in a patient with Merkel cell carcinoma, and a disease control rate of 68% (J Clin Oncol 42, 2024 (suppl 16; abstr 2520); NCT03922204).	detail...
CD274 positive	Advanced Solid Tumor	predicted - sensitive	MCLA-145	Phase I	Actionable	In a Phase I trial, MCLA-145 treatment demonstrated safety and activity in patients with CD274 (PD-L1)-positive advanced solid tumors (n=52), resulting in 5 partial responses (1 each in glioblastoma, sarcoma, cervical cancer, anal cancer, and gastric cancer) and a disease control rate of 37% (J Clin Oncol 42, 2024 (suppl 16; abstr 2520); NCT03922204).	detail...