Immatics Announces Updated Phase 1b Clinical Data on ACTengine® IMA203 TCR-T Targeting PRAME in Melanoma Patients and Provides Update on Upcoming SUPRAME Phase 3 Trial
Immatics announced updated Phase 1b clinical data on ACTengine® IMA203 TCR-T targeting PRAME in 28 heavily pretreated metastatic melanoma patients. Key findings include:
- Confirmed objective response rate of 54% with median duration of response of 12.1 months
- Median progression-free survival (PFS) of 6 months
- Favorable tolerability profile maintained
- Patients with deep responses show median PFS of more than one year
Based on these results, Immatics will proceed to a registration-enabling Phase 3 trial called 'SUPRAME'. This trial will enroll 360 patients with unresectable or metastatic melanoma post-treatment with a checkpoint inhibitor. The primary endpoint for full approval will be median PFS. The trial is set to commence in December 2024, with enrollment forecasted to complete in 2026.
Immatics ha annunciato dati clinici aggiornati della Fase 1b sul ACTengine® IMA203 TCR-T che mira a PRAME in 28 pazienti affetti da melanoma metastatico con un ampio trattamento pregresso. I risultati chiave includono:
- Tasso di risposta oggettiva confermata del 54% con una durata mediana della risposta di 12,1 mesi
- Sopravvivenza libera da progressione (PFS) mediana di 6 mesi
- Profilo di tollerabilità favorevole mantenuto
- I pazienti con risposte profonde mostrano una PFS mediana di più di un anno
In base a questi risultati, Immatics procederà con un trial di Fase 3 abilitante alla registrazione chiamato 'SUPRAME'. Questo studio arruolerà 360 pazienti con melanoma non resecabile o metastatico dopo trattamento con un inibitore del checkpoint. L'obiettivo primario per l'approvazione completa sarà la PFS mediana. Lo studio è previsto per iniziare a dicembre 2024, con l'arruolamento previsto di completarsi nel 2026.
Immatics anunció datos clínicos actualizados de la Fase 1b sobre ACTengine® IMA203 TCR-T que apunta a PRAME en 28 pacientes con melanoma metastásico con tratamiento previo intensivo. Los hallazgos clave incluyen:
- Tasa de respuesta objetiva confirmada del 54% con una duración media de respuesta de 12,1 meses
- Supervivencia libre de progresión (PFS) media de 6 meses
- Perfil de tolerancia favorable mantenido
- Los pacientes con respuestas profundas muestran una PFS mediana de más de un año
Basado en estos resultados, Immatics procederá a un ensayo de Fase 3 habilitante para la registración llamado 'SUPRAME'. Este ensayo inscribirá 360 pacientes con melanoma irresecable o metastásico tras tratamiento con un inhibidor de checkpoint. El objetivo primario para la aprobación total será la PFS mediana. Se espera que el ensayo comience en diciembre de 2024, con previsión de completar la inscripción en 2026.
Immatics는 28명의 강력한 치료를 받은 전이성 흑색종 환자를 대상으로 한 ACTengine® IMA203 TCR-T의 1b 단계 임상 데이터 업데이트를 발표했습니다. 주요 발견 사항은 다음과 같습니다:
- 확인된 객관적인 반응률 54%와 반응 지속 기간의 중앙값 12.1개월
- 중앙 무진행 생존 기간(PFS) 6개월
- 유지된 유리한 내약성 프로파일
- 깊은 반응을 보인 환자들은 중앙 PFS가 1년 이상입니다.
이 결과를 바탕으로 Immatics는 'SUPRAME'이라는 등록 가능 3상 시험을 진행할 것입니다. 이 시험은 체크포인트 억제제로 치료 후 불가수술성 또는 전이성 흑색종 환자 360명을 모집합니다. 전체 승인에 대한 주요 목표는 중앙 PFS입니다. 시험은 2024년 12월에 시작될 예정이며, 2026년까지 모집 완료가 예상됩니다.
Immatics a annoncé des données cliniques mises à jour de la Phase 1b concernant ACTengine® IMA203 TCR-T ciblant PRAME chez 28 patients atteints de mélanome métastatique fortement prétraités. Les principales conclusions incluent :
- Taux de réponse objective confirmé de 54% avec une durée médiane de réponse de 12,1 mois
- Survie sans progression médiane (PFS) de 6 mois
- Profil de tolérance favorable maintenu
- Les patients ayant des réponses profondes présentent une PFS médiane de plus d'un an
Sur la base de ces résultats, Immatics procédera à un essai de Phase 3 habilitant à l’enregistrement appelé 'SUPRAME'. Cet essai recrutera 360 patients présentant un mélanome non résécable ou métastatique après traitement par un inhibiteur de point de contrôle. Le critère principal pour l'approbation complète sera la PFS médiane. L'essai devrait commencer en décembre 2024, avec une prévision de clôture des recrutements en 2026.
Immatics hat aktualisierte klinische Daten der Phase 1b zu ACTengine® IMA203 TCR-T vorgestellt, die sich auf PRAME bei 28 stark vorbehandelten Patienten mit metastasiertem Melanom konzentrieren. Zu den wichtigsten Ergebnissen gehören:
- Bestätigte objektive Ansprechrate von 54% mit einer medianen Ansprechdauer von 12,1 Monaten
- Medianes progressionsfreies Überleben (PFS) von 6 Monaten
- Erhalt eines günstigen Verträglichkeitsprofils
- Patienten mit tiefen Ansprechen weisen ein medianes PFS von mehr als einem Jahr auf.
Basierend auf diesen Ergebnissen wird Immatics zu einer registrierungsfähigen Phase-3-Studie mit dem Namen 'SUPRAME' übergehen. Diese Studie wird 360 Patienten mit nicht resezierbarem oder metastasierendem Melanom nach Behandlung mit einem Checkpoint-Inhibitor rekrutieren. Der primäre Endpunkt für die vollständige Genehmigung wird das mediane PFS sein. Die Studie soll im Dezember 2024 beginnen, und die Rekrutierung wird voraussichtlich 2026 abgeschlossen sein.
- Confirmed objective response rate of 54% with median duration of response of 12.1 months in Phase 1b
- Median progression-free survival (PFS) of 6 months, comparing favorably to Phase 1a median PFS of 2.6 months
- Patients with deep responses show median PFS of more than one year
- Favorable tolerability profile maintained across all dose levels
- Proceeding directly to a registration-enabling Phase 3 trial based on positive Phase 1b data
- FDA agreement on using median PFS as primary endpoint for full approval, potentially expediting the approval process
- Median overall survival not yet reached, indicating need for longer follow-up
- Phase 3 trial enrollment not expected to complete until 2026, suggesting a lengthy timeline to potential approval
Insights
The updated Phase 1b data for ACTengine® IMA203 in melanoma patients shows promising results:
- 54% confirmed objective response rate with 12.1 months median duration of response
- 6 months median progression-free survival (PFS), compared to 2.6 months in Phase 1a
- Median overall survival not yet reached
- Favorable safety profile maintained
The data supports advancing to a Phase 3 trial (SUPRAME) with PFS as the primary endpoint for full approval. Key points:
- 360 patients with 2L+ metastatic melanoma
- Randomized 1:1 vs. investigator's choice
- Trial to start December 2024, enrollment complete 2026
- Interim analysis planned for early 2026
This accelerated development path and robust data could position IMA203 as a promising new option for advanced melanoma patients. The
The clinical data for IMA203 in melanoma is encouraging, particularly given the heavily pretreated patient population. Key observations:
- Durable responses across melanoma subtypes, including difficult-to-treat uveal melanoma
- Median PFS of 13.4 months in patients with >
50% tumor reduction - T cell persistence for over 2 years, suggesting potential for long-term efficacy
- Correlation between T cell dose/exposure and clinical responses
The favorable safety profile is notable, with manageable cytokine release syndrome and low rates of severe neurotoxicity. This could differentiate IMA203 from other cell therapies.
The planned Phase 3 trial design aligns well with regulatory expectations and could support a broad label in 2L+ melanoma if successful. However, manufacturing consistency and durability of responses in a larger patient population will be critical to watch in the pivotal trial.
Company to host conference call and webcast today, October 10, at 9:00 am EDT/3:00 pm CEST
- Company announces updated Phase 1b clinical data on ACTengine® IMA203 targeting PRAME in 28 heavily pretreated metastatic melanoma patients with substantially enhanced maturity compared to the last data update in May 2024 and provides the first report on progression-free survival (PFS) and overall survival (OS)
- Based on the Phase 1b data, the Company will proceed directly to a registration-enabling Phase 3 trial
- Regulatory pathway and clinical trial design for IMA203 finalized following FDA Type D meetings and meeting with the Paul Ehrlich Institute (PEI); RP2D and CMC package confirmed
- IMA203 continues to maintain a favorable tolerability profile in patients in Phase 1a and Phase 1b treated across all dose levels
- IMA203 demonstrates a confirmed objective response rate of
54% with median duration of response of 12.1 months in Phase 1b - Median PFS is 6 months, comparing favorably to the IMA203 Phase 1a dose escalation median PFS of 2.6 months; patients with deep responses show median PFS of more than one year; median OS not reached
- Phase 3 trial, “SUPRAME,” will enroll 360 patients with unresectable or metastatic melanoma post treatment with a checkpoint inhibitor (2L+) and will randomize patients 1:1 for treatment with IMA203 or investigator’s choice
- Primary endpoint for full approval will be median PFS, which constitutes the fastest pathway to registration in this patient population
- SUPRAME Phase 3 trial is on track to commence in December 2024; enrollment forecasted to be completed in 2026 with a pre-specified interim analysis planned for early 2026
- Conference call and webcast can be accessed here
Houston, Texas and Tuebingen, Germany, October 10, 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 updated Phase 1b clinical data on ACTengine® IMA203 TCR-T targeting PRAME in melanoma patients and provided an update on SUPRAME, the upcoming Phase 3 trial to evaluate IMA203 in metastatic melanoma patients.
The data from the ongoing Phase 1b trial will be presented on Friday, October 11, 2024, by Martin Wermke, M.D., during Plenary Session 1, Developmental Immunotherapy (Cellular Immunotherapy, Vaccines, & New Checkpoints) at the Society for Melanoma Research Congress 2024. The IMA203 data slides are accessible in the ‘Events & Presentations’ section of the Investor & Media section of the Company’s website. The conference presentation will include additional patient cases.
“Observing significant tumor shrinkage and durable responses combined with meaningful progression-free survival and overall survival outcomes after a single treatment with ACTengine® IMA203 in this patient population that have all exhausted multiple lines of systemic treatments illustrates the impact IMA203 can have on metastatic melanoma patients,” said Martin Wermke, M.D., Coordinating Investigator of the ACTengine® IMA203 TCR-T trial. “These results now affirm the therapeutic potential of IMA203 and provide a strong rationale for the expedited late-stage clinical development of this product candidate.”
“We are enthusiastic about the clinical data as they confirm our conviction in the durability and long-term efficacy of ACTengine® IMA203, demonstrated by the favorable median progression-free survival for patients in the dose expansion cohort. I would like to highlight that a subgroup of 12 out of 26 patients showed more than
Patient Population and Clinical Data Summary - ACTengine® IMA203 Monotherapy Phase 1b Trial
Patient population: Heavily pretreated metastatic melanoma patients
As of August 23, 2024, 28 heavily pretreated patients with metastatic melanoma were treated at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells) with IMA203 during the Phase 1b dose expansion part of the clinical trial. The treated patient population is composed of patients with a median of 2 lines of prior systemic treatments, consisting of cutaneous melanoma patients (N=13), uveal melanoma patients (N=12), mucosal melanoma patients (N=2) and a patient with melanoma of unknown primary (N=1).
Safety: Favorable tolerability profile demonstrated across all dose levels in Phase 1a and Phase 1b
IMA203 monotherapy has maintained a favorable tolerability profile with no treatment-related Grade 5 adverse events in the safety population (N=701 Phase 1a and Phase 1b patients across all dose levels and all tumor types), even at doses up to ~10x109 TCR-T cells.
The most frequent adverse events were expected cytopenias (Grade 1 – 4) associated with lymphodepletion as well as mostly mild to moderate cytokine release syndrome (CRS). Some patients infrequently experienced ICANS (Grade 1:
The full IMA203 monotherapy tolerability profile is also generally consistent with that observed in the Phase 1b melanoma subset.
Anti-tumor activity and durability: Durable objective responses in melanoma patients at RP2D3
This data update adds substantial maturity to the most recent data update from May 2024 (data cut-off on April 25, 2024). The median follow-up for the median duration of response for this analysis was 9.3 months compared to 3.5 months in May 2024.
| All melanoma patients in Phase 1b (N=282,3) | Cutaneous melanoma patients in Phase 1b (N=133) | |
| Confirmed Objective Response Rate | | |
| Objective Response Rate | | |
| Disease Control Rate | | |
| Tumor Shrinkage | | |
| Median Duration of Response | 12.1 months | 12.1 months |
| Median Progression-Free Survival | 6.0 months | 6.1 months |
| Median Overall Survival | Not reached | 15.9 months |
Progression-free survival (PFS) and overall survival (OS): Significant shift in PFS and OS between Phase 1a dose escalation to Phase 1b dose expansion in melanoma patients
Manufacturing improvements were implemented prior to the Phase 1b part of the trial to enhance key features of IMA203. As a result, all patients in dose expansion were treated with an updated version of IMA203 that includes a T cell enrichment process using monocyte depletion (negative selection) or CD8/CD4 positive selection.
The data presented today demonstrate a significant positive shift in median PFS and median OS between melanoma patients treated during Phase 1a and patients treated in Phase 1b.
| Phase 1b dose expansion melanoma patients (N=28) | Phase 1a dose escalation melanoma patients (N=11) | |
| Median Progression-Free Survival | 6.0 months | 2.6 months |
| Median Overall Survival | Not reached | 6.3 months |
In addition, approximately half of all patients in the Phase 1b trial have a deep response (>
Translational data: IMA203 T cell dose and T cell exposure are associated with clinical responses
Translational data from patients across Phase 1a and Phase 1b indicate that IMA203 T cells rapidly engrafted in all patients after a single dose and show a persistence of more than two years. Three associations/correlations were observed demonstrating high consistency of dose exposure, biological data and clinical outcome in all patients treated with IMA203 for which samples were available (N=65):
- IMA203 T cell dose is significantly associated with confirmed clinical responses (p=0.02),
- IMA203 T cell dose is correlated with T cell peak level (cmax, r=0.84, p=1.6x10-18),
- IMA203 T cell peak level (cmax, p=0.05) and T cell exposure (AUC0-28d, p=0.05) are associated with confirmed clinical responses.
Development Path and Manufacturing for ACTengine® IMA203 Monotherapy
On September 24, 2024, Immatics completed a Type D meeting with the U.S. Food and Drug Administration (FDA) to confirm RP2D and the CMC package as well as discuss the trial design for SUPRAME, the planned registration-enabling Phase 3 randomized-controlled clinical trial for IMA203. Written post-meeting minutes from the FDA have been received.
The Phase 3 trial 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.
Based on the Company’s discussions with the FDA, the primary endpoint for full approval will be median PFS. Given the expected PFS of 2-3 months4 in this patient population, as well as the PFS of 6 months observed in the data from the IMA203 Phase 1b trial, the Company has determined that utilizing median PFS as the primary endpoint is the fastest pathway to seeking full approval and presents a more attractive commercial positioning as compared to objective response rate (ORR). Secondary endpoints for the trial will include ORR, safety, duration of response, no overall survival detriment and patient-reported outcomes. A pre-specified interim analysis is planned for early 2026.
The SUPRAME Phase 3 trial is planned to run globally with sites in the United States and Europe with the initial goal of seeking Biologics License Application (BLA) approval in the United States. On October 2, 2024, Immatics also completed a meeting with the Paul Ehrlich Institute (PEI), the German regulatory authority, and determined the same trial design for conducting the clinical trial in Germany.
The Phase 3 trial is on track to commence in December 2024 and patient enrollment is forecasted to be completed in 2026. The Company aims to submit a BLA in early 2027 for full approval.
Immatics’ late-stage clinical cell therapy development is supported by its differentiated manufacturing related to timeline, capabilities and facilities. ACTengine® IMA203 cell therapy products are manufactured within 7 days, followed by a 7-day QC release testing at a success rate of >
Immatics Conference Call and Webcast
Immatics will host a conference call and webcast today, October 10, 2024, at 9:00 am EDT/ 3:00 pm CEST to discuss the clinical data.
A replay of the webcast will be made available shortly after the conclusion of the call and archived on the Immatics website for at least 90 days.
About ACTengine® IMA203 and Target PRAME
ACTengine® IMA203 is Immatics’ most advanced TCR-based autologous cell therapy that is directed against an HLA-A*02-presented (human leukocyte antigen) peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers. PRAME is homogeneously and specifically expressed in tumor tissue and Immatics’ PRAME peptide is present at a high copy number per tumor cell. 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®, Immatics has generated a highly specific T cell receptor (TCR) against this target for ACTengine® IMA203.
ACTengine® IMA203 TCR-T is currently being evaluated as a monotherapy in a Phase 1 clinical trial in patients with solid tumors expressing PRAME, such as cutaneous melanoma. An IMA203 registration-enabling randomized controlled Phase 3 trial, “SUPRAME,” is planned to commence in December 2024.
ACTengine® IMA203 TCR-T is also currently being evaluated in Phase 1 IMA203CD8 (GEN2) monotherapy, where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor.
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About Immatics
Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.
Immatics intends to use its website www.immatics.com as a means of disclosing material non-public information. For regular updates you can also follow us on X, Instagram and LinkedIn.
Forward-Looking Statements
Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or the Company’s future financial or operating performance. For example, statements concerning timing of data read-outs for product candidates, the timing, outcome and design of clinical trials, the nature of clinical trials (including whether such clinical trials will be registration-enabling), the timing of IND or CTA filing for pre-clinical stage product candidates, the timing of BLA filings for clinical stage product candidates, estimated market opportunities of product candidates, manufacturing timetables, capacity and success rates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “plan”, “target”, “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 Immatics and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission (SEC). Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. The Company undertakes no duty to update these forward-looking statements. All the scientific and clinical data presented within this press release are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification.
For more information, please contact:
| Media | |
| Trophic Communications | |
| Phone: +49 171 3512733 | |
| immatics@trophic.eu |
| Immatics N.V. | |
| Jordan Silverstein | |
| Head of Strategy | |
| Phone: +1 346 319-3325 | |
| InvestorRelations@immatics.com |
1 All patients who started lymphodepletion. Includes one patient who started lymphodepletion but did not receive IMA203 TCR-T cells and one patient who started lymphodepletion with T cell infusion scheduled after data-cut.
2 First tumor assessment post infusion pending for additional two melanoma patients at data-cut.
3 Melanoma efficacy population excludes 5 patients treated at DL4 in Phase 1a of the trial as reported in the May 2024 update, based on different manufacturing version used that affects the T cell product. See the IMA203 data presentation slides available on the Immatics website for more detailed information and a patient population flow chart.
4 See the IMA203 data presentation slides available on the Immatics website for more detailed information and an overview of studies.
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FAQ
What were the key results of Immatics' Phase 1b trial for IMA203 in melanoma patients?
When is Immatics (IMTX) planning to start the Phase 3 SUPRAME trial for IMA203?
What is the primary endpoint for the Phase 3 SUPRAME trial of IMA203?
How does the safety profile of IMA203 look based on the Phase 1b data?
