Company to host conference call on
- Dose escalation for cell therapy candidate ACTengine® IMA203 ongoing; dose level 3 completed at doses below 1 billion transduced cells
- Objective responses (RECIST 1.1) observed in 8/16 patients (50%) across multiple solid cancer types, with 8/13 responders (62%) treated at dose levels 2 and 3
- High T cell engraftment and persistence; clinical response associated with tumor infiltration
- Transient and manageable treatment-emergent adverse events; no higher-grade cytokine release syndrome or neurological toxicities observed
- IMA203 clinical data will be presented as late-breaking oral presentation at the SITC Annual Meeting on
Saturday, November 13 at12:00 pm EST
Key clinical findings from IMA203 Phase 1a trial
In the ongoing ACTengine® IMA203 trial,
Clinical and biological activity: IMA203 demonstrates objective responses (RECIST 1.1.) at low cellular doses across several solid cancer types
- At data cut-off on
October 5, 2021 , 18 patients received ACTengine® IMA203 T cells across dose level 1 (DL1) to dose level 4 (DL4). - All patients were heavily pretreated with a median of 4 lines of prior systemic treatment.
- 16 patients were evaluable for tumor response analysis according to RECIST 1.1 with at least one post-treatment tumor assessment at the time of data cut-off. All 16 patients received dose levels 1 to 3 - below 1 billion total transduced cells. For the remaining 2 patients, the first tumor response assessment is still pending.
- 15 out of 16 patients (94%) achieved disease control. Tumor shrinkage was observed in 14 patients (88%).
- 8 out of 16 patients (50%) showed objective responses; onset of responses in all cases was detected within 6 weeks following infusion of IMA203 T cells.
- All responses occurred above DL1; 8 out of 13 patients (62%) treated at DL21 and DL3 receiving up to 0.59 billion total transduced cells had objective partial responses. Responses were observed in patients with synovial sarcoma, malignant melanoma, uveal melanoma, and head and neck cancer.
- As of data cut-off, partial responses were confirmed in subsequent scans in two synovial sarcoma patients and one uveal melanoma patient.
- Longer follow-up is required for patients infused at higher dose levels DL3 and DL4 are required to assess response durability and response rate at target dose.
- IMA203 continues to show high levels of T cell engraftment, persistence, and tumor infiltration at first three dose levels. Clinical response was associated (p=0.016) with infiltration of IMA203 T cells into the tumor tissue and showed an emerging trend towards higher peak vector copies of IMA203 T cells in blood (p=0.065) – supporting the mechanism-of-action.
- The ACTengine® IMA203 trial is currently recruiting patients to the 4th and highest dose level (up to approximately 2.5 billion total transduced cells) of the Phase 1a dose escalation cohort.
Preliminary Objective Response Rates (ORR; RECIST 1.1, confirmed and unconfirmed)
| Dose Level | ORR |
| DL1 | 0/3 (0%) |
| DL21 | 6/10 (60%) |
| DL3 | 2/3 (67%) |
| All dose levels | DL21 & DL3 | |
| All comers | 8/16 (50%) | 8/13 (62%) |
| Melanoma | 3/3 (100%) | 3/3 (100%) |
| Head & Neck Cancer | 1/3 (33%) | 1/1 (100%) |
| Synovial Sarcoma | 3/5 (60%) | 3/5 (60%) |
| Uveal Melanoma | 1/2 (50%) | 1/2 (50%) |
Safety: IMA203 treatment was well tolerated with transient and manageable treatment-emergent adverse events (TEAEs)
- At data cut-off on
October 5, 2021 , 19 patients were evaluable for safety analysis. - Most frequent TEAEs included expected transient cytopenia (Grade 1-4) associated with lymphodepletion and transient low to moderate (Grade 1-2) cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS).
- No additional dose limiting toxicities (DLT) were observed since the previous data release on
March 17, 2021 .
“We observed multiple clinical responses early-on during dose escalation and saw anti-tumor activity at much lower doses than would have been expected in the field of TCR-T. IMA203 T cells will now be tested at the target dose level and have the potential to provide meaningful benefits to patients with advanced stages of cancer,” commented
Following the completion of the dose escalation portion of the study (Phase 1a) and the determination of the recommended Phase 2 dose (RP2D),
- IMA203 as a monotherapy
- IMA203 in combination with an immune checkpoint inhibitor
- IMA203CD8, next-generation TCR-T where IMA203 cells are co-transduced with a CD8 co-receptor
Preclinical update on next-generation ACTengine® IMA203CD8
IMA203CD8 consists of IMA203-engineered T cells targeting PRAME co-transduced with CD8αβ T cell co-receptor that plays an important role during T cell antigen recognition and T cell activation. The IMA203CD8 product candidate has the potential to harness the potency of CD4 T cells. Engagement of CD4 T cells, in addition to CD8 T cells, might further enhance depth and durability of anti-tumor response and clinical outcome of TCR-T in solid cancer patients.
Immatics has exclusively licensed the CD8αβ technology fromBaylor College of Medicine inHouston, Texas .- IMA203CD8 product candidate demonstrates enhanced anti-tumor activity in preclinical proof-of-concept data, which will be presented on-site at the SITC Annual Meeting on
Friday, November 12, 2021 between7 am - 8:30 pm EST as well as virtually throughout the duration of the conference. The poster will also be available on Immatics’ website following the poster presentation. - IND submission for IMA203CD8 cohort is expected in the first half of 2022.
Further updates on the ACTengine® IMA200 Programs
IMA201 (MAGEA4/A8) and IMA202 (MAGEA1)
- The dose escalation Phase 1a study with ACTengine® IMA201 and IMA202 product candidates directed at MAGEA4/8 and MAGEA1 HLA-A*02 peptides respectively, continue to advance with IMA202 at dose level 3 and IMA201 at dose level 2.
- At data cut-off on
September 17, 2021 , 12 heavily pretreated patients have been treated; 8 out of 12 patients showed disease control. Tumor shrinkage was observed in 6 patients. - All treatment-emergent adverse events (TEAEs) for both IMA201 and IMA202 continue to be transient and manageable. No dose limiting toxicities (DLT) or higher grade CRS/ICANS have been observed.
- The next step in the IMA201 and IMA202 trials is to complete dose escalation including target dose (DL3).
IMA204 (COL6A3 exon 6)
- ACTengine® IMA204 is a potential first-in-class TCR-T directed against COL6A3 exon 6, a novel tumor stroma target highly expressed in several solid cancers. IMA204 utilizes a next-generation CD8-independent TCR with full functionality in both CD4 and CD8 T cells.
- IND-enabling studies are close to completion. Submission of the IND application for IMA204 is now expected in 2022 to allow accelerated initiation of the multiple ACTengine® IMA203 Ph1b cohorts.
1DL2 here includes patients dosed with DL2, EC1 and EC2 (EC1: Enrichment cohort with intermediate dose level between DL1 and DL2 , EC2: between DL2 and DL3)
About Immatics’ PRAME Programs
Immatics’ PRAME programs are directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers – such as uterine carcinoma, synovial sarcoma, melanoma, ovarian carcinoma, uveal melanoma, squamous NSCLC, breast carcinoma and HNSCC – thereby supporting the programs’ potential to address a broad cancer patient population. Immatics’ PRAME peptide demonstrates a high copy number per tumor cell and is homogenously and specifically expressed in tumor tissue. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform XPRESIDENT®. Through its proprietary TCR discovery and engineering platform XCEPTOR®, the Company has generated a highly specific T cell receptor (TCR) against this target for its TCR-based cell therapy approach, ACTengine® IMA203, and its TCR Bispecifics pipeline, TCER® IMA402. Both therapeutic modalities have distinct attributes and mechanisms of actions suitable for cancer patients at different disease stages and tumor types.
ACTengine® IMA203 is currently being evaluated in an ongoing Phase 1a dose escalation cohort utilizing a 3+3 design with four increasing IMA203 dose levels to determine the Recommended Phase 2 Dose (RP2D).
TCER® IMA402 is a PRAME-specific “off-the-shelf” biologic that leverages the body’s immune system by redirecting and activating T cells towards cancer cells. TCER® IMA402 has previously demonstrated anti-tumor activity against PRAME-positive cancer cells in an in vivo mouse model leading to consistent tumor regression including complete responses.
About ACTengine® programs
ACTengine® is a personalized approach for patients with advanced solid tumors. The patient’s own T cells are genetically engineered to express a novel, proprietary TCR directed against a defined cancer target. The modified T cells are then reinfused into the patient to attack the tumor, an approach also known as TCR-T. ACTengine® programs IMA201 (NCT03247309), IMA202 (NCT03441100) and IMA203 (NCT03686124) are currently in clinical development in the US and in
The ACTengine® T cell products are manufactured at the
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Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or Immatics’ future financial or operating performance. For example, statements concerning the timing of product candidates and Immatics’ focus on partnerships to advance its strategy are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by
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1 DL2 here includes patients dosed with DL2, EC1 and EC2 (EC1: Enrichment cohort with intermediate dose level between DL1 and DL2 , EC2: between DL2 and DL3)
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