- STARt-001 is the first clinical study to evaluate Marengo's
novel, selective Vβ TCR agonist technology to promote in vivo
expansion and reprogramming of tumor-infiltrating lymphocytes
(TILs) in patients with advanced cancers
- Invikafusp alfa, a first-in-class, TCR Vβ6/Vβ10 selective
dual T cell agonist, as a single agent, demonstrated tumor
shrinkage across multiple tumor types with a manageable safety
profile in heavily pre-treated, anti-PD-1 resistant patients
- Clinical activity of invikafusp alfa observed in cancers
with high tumor mutation burden (TMB-H) including confirmed
responses in microsatellite stable (MSS) colorectal cancer
CAMBRIDGE, Mass., Nov. 9, 2024
/PRNewswire/ -- Marengo Therapeutics, Inc., a clinical-stage
biotechnology company pioneering novel approaches for precision T
cell activation, today announced encouraging initial Phase 1
clinical data from its lead program, invikafusp alfa (STAR0602),
during a late-breaking oral presentation at the Society
for Immunotherapy of Cancer (SITC) 39th Annual Meeting taking
place in Houston, Texas.
This is the first public disclosure of results from the ongoing
STARt-001 Phase 1/2 trial (NCT05592626), evaluating invikafusp alfa
as monotherapy in biomarker-enriched (TMB-H, MSI-H/dMMR or virally
associated) patients with advanced anti-PD-1 resistant, or
refractory solid tumors.
Phase 1 data from STARt-001 trial demonstrate early anti-tumor
activity, including initial signals of clinical benefit in heavily
pre-treated, anti-PD-1 resistant cancer patients. Invikafusp alfa
also showed a manageable safety profile consistent with its novel
mechanism of action, further supporting its potential as a
treatment option across a range of high tumor mutational burden
(TMB-H) cancers or virally associated malignancies.
"Having completed Phase 1 and commenced the Phase 2 dose
expansion cohorts of STARt-001, Marengo is thrilled to share
initial clinical findings that validate our novel selective dual T
cell agonist platform," said Zhen
Su, M.D., MBA, Chief Executive Officer of Marengo
Therapeutics. "The single agent activity observed in Phase 1,
especially in PD-1 resistant cold tumors such as colorectal cancer
is a critical milestone, and we look forward to further exploring
the potential of STAR0602 to become a next-generation backbone IO
therapy across a range of tumor types."
Additional highlights from the Phase 1 findings include:
- Sustained and selective in vivo expansion of TCRVβ6/Vβ10
T cells was achieved across all 6 dose levels with up to ~500% peak
increase post invikafusp alfa treatment
- Disease Control Rate (PR + SD) was reported in 50% of 28
patients from all dose escalation cohorts with 32% of patients
experienced tumor shrinkage across six tumor types
- At the optimal biological dose range (0.08 mg/kg and 0.12
mg/kg), invikafusp alfa had single agent clinical activity with 63%
Disease control rate, 50% of patients experienced tumor shrinkage
and 25% ORR reported in TMB-H, anti-PD-1 resistant patients
- Safety profile was consistent with the T cell
activation/expansion mechanism of action (MOA) without
corticosteroid or tocilizumab pretreatment. The most common
treatment-related adverse events (TRAEs) were mainly transient
grade 1 & 2 CRS during first and second infusion without any
grade 4 adverse events (AEs) or immune effector cell-associated
neurotoxicity syndrome (ICANS)
- Recommended Phase 2 dose (RP2D) of 0.08 mg/kg was selected for
Phase 2 dose expansion studies based on safety, PK/PD data and
preliminary anti-tumor activity
"The first-in-human data suggest that this novel approach to
selectively activate and expand Vβ T cell subsets may hold
promise for treating patients with advanced solid tumors," said Dr.
James L. Gulley, Co-Director of the
Center for Immuno-Oncology and Clinical Director of the National
Cancer Institute. "The observed unique Vβ T cell biology in humans
and selective expansion of Vβ6/Vβ10 across a range of solid tumors,
combined with the initial anti-tumor activity, particularly in
heavily pre-treated anti-PD-1 resistant cancer patients with TMB-H
colorectal cancer, are encouraging signs. The differentiated
clinical profile supports further investigation of this unique
mechanism of action in the next phase of clinical trials for high
unmet medical needs in anti-PD-1 resistant tumors."
Taken together, the data presented from the STARt-001 study
underscore invikafusp alfa's potential as a novel therapeutic
option for patients with advanced, PD-1-resistant solid tumors.
Marengo has initiated the Phase 2 dose expansion and expects to
share initial results in 2H 2025.
Late-breaking oral presentation details:
- Title: A Phase 1/2 study of Invikafusp alfa (STAR0602),
a first-in-class TCR β chain-targeted bispecific antibody, as
monotherapy in patients with antigen-rich solid tumors resistant to
anti-PD(L)1.
- Conference: 39th SITC Annual Meeting.
- Abstract Number: LBA-1470.
- Session Title: Late-Breaking Abstract Session 2.
- Session Date and Time: Saturday,
November 9, 2024, 11:45 AM - 12:15
PM.
- Presenter: James L.
Gulley, M.D., Ph.D. (National Cancer Institute, Bethesda, Maryland, USA).
About Marengo Therapeutics
Marengo Therapeutics, Inc,
a clinical-stage biotech company, develops novel TCR-targeting
antibodies that selectively modulate common and disease-specific T
cell subsets of the germline TCR repertoire to provide lifelong
protection against cancer and other diseases. With a passionate
team of dedicated scientists experienced in immunology and
oncology, Marengo's proprietary Selective T Cell Activation
Repertoire (STAR) platform leverages an extensive biological
understanding of T cell function and receptor signaling to create a
world in which everyone's immune system can defeat cancer. To learn
more, visit marengotx.com.
About STAR™ Platform
Marengo's
STAR™ Platform is a multi-specific antibody-fusion
platform derived from Marengo's proprietary library of antibodies
targeting germline-encoded variable Vβ regions of the TCR fused to
different T cell co-stimulatory moieties. Combining a novel
non-clonal mode of TCR activation with a T cell co-stimulator in
the same molecule, promotes a distinct mechanism of action that
promotes durable anti-tumor Vβ T cell responses.
About invikafusp alfa (STAR0602)
Invikafusp alfa
(STAR0602) is Marengo's lead program, the first T cell activator
generated from Marengo's STAR platform; a library of antibodies
targeting non-clonal variable Vβ regions of the TCR fused to
different co-stimulatory moieties. STAR0602 selectively targets a
common Vβ T cell subset present in all cancers and, by combining a
novel non-clonal mode of TCR activation with a T cell co-stimulator
in the same molecule, promotes expansion of a new population of
clonally enriched, effector memory Vβ T cells that turbo-charge
tumor immune responses and promote durable clearance of tumors.
STAR0602 has undergone extensive preclinical testing and is
currently being studied in a Phase 1/2 clinical trial.
About the STARt-001
STARt-001 is a Phase 1/2 clinical
trial evaluating the safety, tolerability, and preliminary clinical
activity of invikafusp alfa (STAR0602) as a single agent in
biomarker selected patients with advanced antigen-rich solid tumors
including PD-1 refractory and rare tumors. This open-label,
multi-center trial consists 2 of two parts: Phase 1 dose escalation
and Phase 2 dose expansion. For more information, please visit
clinicaltrials.gov (trial identifier: NCT05592626).
For patients interested in enrolling in this study at NCI,
please contact NCI's toll-free number 1800-4-Cancer
(1-800-422-6237) (TTY: 1-800-332-8615) and/or the
website https://trials.cancer.gov and/or email
NCIMO_referrals@mail.nih.gov.
Marengo Contacts:
Media
Peg Rusconi I
peg.rusconi@deerfieldgroup.com
Investors
Svetlana
Makhni | smakhni@marengotx.com
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