Full Press Release Details
Immatics Announces Multiple Presentations at
39th Annual Meeting of the Society
for Immunotherapy of Cancer (SITC)
on TCR-T Therapy Candidates Targeting PRAME
presentations and multiple posters on clinical and
preclinical-stage candidates to be presented at SITC, demonstrating
the strength of Immatics' TCR-T PRAME franchise to target solid cancers
Texas and Tuebingen, Germany, November 8, 2024 - Immatics N.V. (NASDAQ:
IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company active in the discovery and development
of T cell-redirecting cancer immunotherapies, today announced an expanded clinical dataset from the ongoing Phase 1b dose expansion clinical
trial for ACTengine IMA203 in addition to updated Phase 1 dose escalation clinical data on its next-generation ACTengine IMA203CD8
TCR-T cell therapy. For the first time, the Company also reported preclinical data on other next-generation T cell candidates and combination
strategies as part of its strategy to further exploit opportunities in additional solid tumor types within its PRAME franchise.
All dates and times of Immatics' upcoming
oral and poster presentations at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) are available here.
are accessible in the Events
& Presentations' section of the Investor & Media section of the Company's website.
"Immatics remains fully focused on the clinical
development of our most advanced lead product candidate, IMA203, in second-line or later metastatic melanoma patients. We look forward
to the initiation of SUPRAME, the registration-enabling Phase 3 trial, in December," said Dr. Cedrik Britten, Chief Medical Officer
at Immatics. "Today, we also provide an update on our first, next-generation cell therapy, IMA203CD8, which is designed to
achieve enhanced anti-tumor activity. The data announced confirm IMA203CD8's enhanced pharmacology and potency per cell in patients.
These attributes highlight the potential of this therapy in hard-to-treat solid tumors with medium-level PRAME copy numbers, including
ovarian, endometrial and triple-negative breast cancer. The next step will be to further increase the cell dose to assess the full clinical
potential of IMA203CD8 beyond melanoma. In addition, we strive to continuously improve the potential therapeutic benefit for patients
with a range of PRAME-positive cancers through the expansion of our PRAME franchise."
ACTengine IMA203 Monotherapy Phase 1b
Trial - Clinical Data and Development Path Summary
On October 10, 2024,
Immatics provided a data update on IMA203 monotherapy in 281
heavily pretreated metastatic melanoma patients from the ongoing Phase 1b dose expansion part of the clinical trial in which patients
were treated at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells).
The data announced today include all infused patients
in the Phase 1b dose expansion part of the trial (N=412),
consisting of the 28 melanoma patients reported on October 10, 2024, and 13 non-melanoma patients, of which 10 non-melanoma patients were
reported on November 8, 2023.
IMA203 monotherapy has maintained a favorable tolerability
profile with no treatment-related Grade 5 events in the entire safety population (N=703
Phase 1a and Phase 1b patients across all dose levels and all tumor types).
Best Overall Response for IMA203 in Dose Expansion
in All Indications (N=41#)
1 Includes one patient who
started lymphodepletion but did not receive IMA203 TCR-T cells.
2 All infused patients, first
tumor assessment post infusion pending for 2/28 melanoma patients at data-cut.
All patients who started lymphodepletion as of the data cut-off on August 23, 2024.
Data cut-off Aug 23, 2024; #First
tumor assessment post infusion pending for 2/28 melanoma patients at data-cut; *Maximum change of target lesions and RECIST1.1 response
at different timepoints. 1Patient A-DL5-23 is off study at data cut-off; 2Patient received one dose nivolumab erroneously.
Development Path for IMA203
Based on the Phase 1b data, the Company is on track
to commence SUPRAME, the registration-enabling Phase 3 randomized-controlled clinical trial in melanoma for IMA203, in December 2024.
SUPRAME will evaluate IMA203 targeting PRAME in
360 HLA-A*02:01-positive patients with second-line or later (2L+) unresectable or metastatic melanoma who have received prior treatment
with a checkpoint inhibitor. Patients will be randomized 1:1 for IMA203 or investigator's choice of selected approved treatments
in the 2L+ setting, including nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US only) or chemotherapy. The primary
endpoint for full approval will be median PFS and secondary endpoints will include objective response rate, safety, duration of response,
no overall survival detriment and patient-reported outcomes.
Patient enrollment for SUPRAME is forecast to be
completed in 2026, and a pre-specified interim analysis is planned for early 2026. Immatics aims to submit a Biologics License Application
(BLA) in early 2027 for full approval.
ACTengine IMA203CD8 (GEN2) Monotherapy
Phase 1 Dose Escalation Trial - Patient Population & Clinical Data Summary
Patient population: Heavily pretreated
patients with solid tumors
As of data cut-off on September 30, 2024, 444
heavily pretreated HLA-A*02:01 and PRAME-positive patients with solid tumors were infused with IMA203CD8 monotherapy across four escalating
dose levels, of which 415 patients were evaluable
for efficacy. The median total infused dose was 1.48x109 TCR-T cells, and the patient population is composed of patients with
a median of three lines of prior systemic treatments.
Safety: Treatment with IMA203CD8 demonstrates
a manageable tolerability profile across dose levels
IMA203CD8 monotherapy has maintained a manageable
tolerability profile in the 44 patients treated. The most frequent adverse events at or above Grade 3 were expected cytopenia associated
with lymphodepletion. Some patients also experienced mild to moderate CRS (Grade 1: 36% Grade 2: 48% Grade 3: 11% Grade 4: 2%).
As previously reported, two patients experienced
dose-limiting toxicities at dose level 4b, which prompted a dosing adjustment to dose level 4a. After further assessing the tolerability
profile of IMA203CD8 in additional patients treated at dose level 4a, the eligibility criteria and the IL-2 dose regimen were modified,
and dose escalation beyond dose level 4a was reinitiated. One Grade 5 adverse event classified as possibly related to treatment with IMA203CD8
was also observed as reported previously in March 2024. The maximum tolerated dose has not yet been determined.
Anti-tumor activity and durability: Deep
and durable objective responses observed
4 All patients who started
5 All infused patients with
at least one tumor assessment postbaseline.
6 Metabolic CR on investigator-initiated
PET month 14 post infusion.
Translational data: Opportunity of IMA203CD8
in medium-level PRAME expressing indications
Translational data indicate that PRAME expression
level is associated with clinical activity in IMA203 and IMA203CD8 treated patients. Both IMA203 and IMA203CD8 achieved deep responses
despite IMA203CD8 patients receiving lower product doses. Based on the enhanced pharmacology of IMA203CD8, the evaluation of higher doses
of IMA203CD8 in the ongoing dose escalation trial opens the possibility of addressing hard-to-treat solid tumor indications with a medium-level
of PRAME copy numbers, such as ovarian cancer, endometrial cancers and triple-negative breast cancer.
Preclinical Data on New Approaches for TCR-T
Based Cell Therapies
As part of Immatics' long-term strategy to
expand its PRAME franchise, the Company has conducted preclinical studies for the potential future clinical development of next-generation
TCR-T-based cell therapies targeting PRAME to further enhance the efficacy and durability of IMA203. These efforts include the evaluation
of TCR-T cells armored with membrane-bound IL-15 (mbIL15) targeting tumor types with low PRAME copy numbers, such as squamous non-small-cell