NGM Bio Presents Preliminary Data from Phase 1 Monotherapy Dose Escalation Trial of NGM707 in Patients with Advanced or Metastatic Solid Tumors at 2022 ESMO-IO Annual Meeting
08 Dec 2022
Phase 1Clinical ResultPhase 2
SOUTH SAN FRANCISCO, Calif., Dec. 07, 2022 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced the presentation of preliminary data from the Phase 1 Part 1a monotherapy dose escalation arm of the ongoing Phase 1/2 trial of NGM707 in patients with advanced or metastatic solid tumors at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Annual Congress, which is taking place December 7 – 9, 2022 in Geneva, Switzerland. In the poster presentation titled, “First-in-Human Study of NGM707, an ILT2/ILT4 Dual Antagonist Antibody in Advanced or Metastatic Solid Tumors: Preliminary Monotherapy Dose Escalation Data” (#174P), NGM707 was generally well tolerated across all dose cohorts and demonstrated promising early signals of anti-tumor activity. Of 24 response-evaluable patients in the Part 1a arm, best overall responses as of November 23, 2022 are partial response in one patient, stable disease in six patients and non-complete response/non-progressive disease in one patient. Six patients had reduced target lesion size including a maximum decrease in one patient of 70%. A copy of the presentation presented at the ESMO I-O Annual Congress is available on NGM Bio’s website at https://www.ngmbio.com/discovery-engine/publications/.
The Phase 1 portion of the ongoing NGM707 trial includes a monotherapy dose escalation arm (Part 1a) and a dose-finding arm in combination with pembrolizumab (KEYTRUDA®) (Part 1b). The Phase 2 portion of the trial will include expansion cohorts of patients treated with NGM707 in combination with KEYTRUDA (Part 2b) in several advanced solid tumor types. The Part 1a arm enrolled patients into escalating NGM707 dose cohorts (6 mg to 1800 mg) administered intravenously every three weeks. Enrolled patients received a median of four prior lines of therapy, and all had metastatic disease. Primary objectives in the Phase 1 portion are to assess safety and tolerability of NGM707 and to identify Phase 2 doses. Secondary/exploratory objectives include assessment of PK/biomarker correlation, immunogenicity, and preliminary antitumor activity per RECIST v1.1.
As of a November 23, 2022 data cut-off, 34 patients have been enrolled in the monotherapy dose escalation. Of 24 response-evaluable patients (those completing at least one on-treatment scan), best overall responses are partial response (PR) in one patient, stable disease in six patients and non-complete response/non-progressive disease in one patient. Six of the 24 response-evaluable patients experienced target lesion reduction. The patient experiencing the PR had a target lesion decrease of 70%, along with a reduction and/or elimination of non-target lesions. These responses were seen across five distinct tumor types. Preliminary evidence of potential myeloid reprogramming was observed in peripheral non-classical monocytes as well as in tumor biopsies, with reduction of the M2 macrophage marker CD163 observed post-treatment. Treatment-related adverse events (TRAEs) occurred in 47% of patients, with 9% of patients experiencing Grade ≥3 TRAEs. One dose-limiting toxicity of pneumonitis (G5) in a patient with pulmonary metastasis was observed at NGM707 600 mg. A maximum tolerated dose was not reached.
As of November 23, 2022, four patients remain on NGM707 monotherapy treatment in the Part 1a arm, including the patient experiencing the PR. Enrollment is ongoing in the Part 1b arm evaluating NGM707 in combination with KEYTRUDA. NGM Bio anticipates enrolling approximately 220 patients in the Phase 1/2 trial of NGM707.
“NGM707 is designed to reprogram immune-suppressive ILT4- and ILT2-expressing myeloid cells and ILT2-expressing lymphoid cells in the tumor microenvironment into immune-stimulatory cells that will promote anti-tumor activity. We’re pleased to present these initial data demonstrating a favorable tolerability profile for NGM707 as well as early, yet promising signals that this mechanistic approach may translate to clinical benefit,” said Dan Kaplan, Ph.D., Head of Translational Immuno-Oncology at NGM Bio. “We’re particularly encouraged to see clinical benefit in certain patients in response to monotherapy treatment with NGM707, and we look forward to evaluating NGM707’s potential effect when combined with T cell checkpoint inhibition in Part 1b of the study, which is now underway.”
About NGM707
ILT2 and ILT4, inhibitory receptors with enriched expression on myeloid cells in the tumor microenvironment, are myeloid checkpoints that may enable certain tumors to evade immune detection, thereby suppressing patients’ anti-tumor responses. NGM707 is being developed with the goal of improving patient immune response to tumors by inhibiting both ILT2 and ILT4. By inhibiting both ILT2 and ILT4, NGM707 may be able to overcome the potential redundant role the two receptors play where they are co-expressed in myeloid cells and reprogram those cells to enhance T cell activity and proliferation. In addition, ILT2 blockade may drive further benefit through reducing suppression in certain lymphoid cells capable of directly attacking tumor cells.
About NGM Bio’s Oncology Portfolio
NGM Bio’s currently disclosed oncology product candidates are all derived from the company’s in-house discovery engine and are wholly owned by NGM Bio. These oncology programs include: NGM120, a GFRAL antagonist antibody in a Phase 2 trial for the treatment of metastatic pancreatic cancer; NGM707, an ILT2/ILT4 (LILRB1/LILRB2) dual antagonist antibody in a Phase 1/2 trial for the treatment of advanced or metastatic solid tumors; NGM831, an ILT3 (LILRB4) antagonist antibody in a Phase 1 trial in advanced solid tumors; and NGM438, a LAIR1 antagonist antibody in a Phase 1 trial in advanced solid tumors.
Abbreviations (in Alphabetical Order)
GFRAL= Glial Cell-derived Neurotrophic Factor Receptor Alpha-like; ILT2=Immunoglobulin-Like Transcript 2; ILT3=Immunoglobulin-Like Transcript 3; ILT4=Immunoglobulin-Like Transcript 4; LAIR1= LAIR1=Leukocyte-Associated Immunoglobulin-Like Receptor 1; LILR=Leukocyte Immunoglobulin-Like Receptor [ILT2 = LILRB1, ILT3=LILRB4, ILT4=LILRB2]; LIR=Leukocyte Immunoglobulin-Like Receptor.
About NGM Bio
NGM Bio is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. The company’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates and enable their rapid advancement into proof-of-concept studies. As explorers on the frontier of life-changing science, NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Today, the company has seven programs in clinical development, including four in Phase 2 or 2b studies, including the recently completed NGM621 CATALINA trial, across three therapeutic areas: cancer, retinal diseases and liver and metabolic diseases. Visit us at www.ngmbio.com for more information.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
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