ITIL-306 / Instil Bio - LARVOL DELTA

ITIL-306 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: Instil Bio | Phase classification: P1a/1b ➔ P1

Metastases • Phase classification • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • ALK • BRCA • EGFR • KRAS

Instil Bio Announces Strategic Update (GlobeNewswire) - "Instil Bio, Inc...announced a strategic update....The feasibility studies have been initiated, and if the feasibility studies are successful, Instil’s collaborator may open an investigator-initiated clinical trial (IIT) to enroll patients with non-small cell lung cancer (NSCLC) in China. In the event the IIT generates compelling proof-of-concept clinical data in 2024, Instil may explore options for a potential transition of ITIL-306 to a US-based CDMO for manufacturing and clinical development primarily at US clinical trial sites."

Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Instil Bio Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Recent Highlights and Anticipated Milestones:...Initial data from ITIL-306-202, a Phase 1 clinical trial of ITIL-306 in non-small cell lung cancer, anticipated in 2024."

P1 data • Non Small Cell Lung Cancer

Instil Bio Announces Poster Presentations of ITIL-306 Preclinical Data at SITC 2023 Annual Meeting (GlobeNewswire) - "New single-cell RNA sequencing data presented at the SITC 2023 Annual Meeting revealed enhanced gene signatures of activation and cytotoxicity in CoStAR-transduced CD4+ T cells, with significant increases in cytotoxic function of these CD4+ T cells in an in vitro cytotoxicity assay. These data suggest that CoStAR is able to endow CD4+ T cells with novel cell-killing capacity, potentially broadening the repertoire of tumor-killing TIL to include CD4+ T cells in addition to naturally cytotoxic CD8+ T cells...CoStAR was demonstrated to enhance the secretion of soluble factors from CD4+ T cells to boost the proliferation and survival of companion CD8+ T cells."

Preclinical • Solid Tumor

Anti-folate receptor alpha (FRα) CoStimulatory Antigen Receptor (CoStAR™) drives distinct cytokine-mediated proliferation responses in CD4+ and CD8+ T cells (SITC 2023) - "Background ITIL-306 is a genetically engineered autologous TIL cell therapy that amplifies TCR-specific antigen recognition signals (Signal 1) with an FRα-specific CoStimulatory Antigen Receptor (CoStAR; Signal 2)...CoStAR engineered CD4+ T cells support CoStAR engineered CD8+ T cells in a contact independent manner. These data support the ability of CoStAR-transduced T cells to proliferate independent of cytokine support, while implying that potential clinical manipulations known to increase the levels of circulating cytokines, such as increasing intensity of lymphodepleting chemotherapy and addition of exogenous IL-2 infusions, could further augment the activity of CoStAR-TILs in vivo."

IO biomarker • Oncology • CD4 • CD40 • CD8 • FOLR1 • IL15 • IL7

Single cell RNA sequencing reveals functionally validated signatures of cytotoxicity in anti-FRα CoStimulatory Antigen Receptor (CoStARTM) activated CD4+ T cells (SITC 2023) - "Background ITIL-306 is a genetically engineered autologous TIL cell therapy that amplifies TCR-specific antigen recognition signals (Signal 1) with an FRα-specific CoStimulatory Antigen Receptor (CoStAR; Signal 2)...Conclusions CoStAR provides functional benefit to both CD4+ and CD8+ T cells in overlapping and distinct ways. Enhancement of CD4+ cytotoxicity by CoStAR was an unexpected, yet intriguing observation which strengthens the rationale for CoStAR engineering approaches for TIL therapy, where CD4+ T cell-mediated anti-tumour responses have been identified as potential drivers of cancer regression in patients."

Oncology • CD4 • CD8 • FOLR1 • HLA-A

Instil Bio Reports Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "ITIL-306, first CoStAR-TIL in clinical development, anticipated to start clinical trial ITIL-306-202 in 2H 2023: Instil anticipates initiating phase 1 clinical trial ITIL-306-202 with an updated trial design versus ITIL-306-201; the ITIL-306-202 trial design has received positive initial feedback from the Medicines and Healthcare products Regulatory Agency, or MHRA in the United Kingdom. Instil expects Clinical Trial Application, or CTA, clearance from the MHRA in the second half of 2023 and initial clinical data from the ITIL-306-202 clinical trial in 2024."

New P1 trial • P1 data • Oncology

Instil Bio Announces Oral Presentation of ITIL-306 Preclinical Data at British Society for Gene and Cell Therapy Annual Conference (GlobeNewswire) - "Instil Bio...reported an oral presentation at the British Society for Gene and Cell Therapy Annual Conference, demonstrating that its proprietary CoStimulatory Antigen Receptor (CoStAR) platform enhances activity of TILs against autologous tumor....Novel data demonstrated that Instil’s FRα-CoStAR enhances activity of TILs against autologous tumors with varied expression of FRα including ovarian, renal, and non-small cell lung cancer tumors. The robust activity of NSCLC, ovarian, and renal carcinoma CoStAR-TILs against autologous tumor exceeded that of genetically unmodified melanoma TILs, as measured by secretion of IFNγ."

Preclinical • Genito-urinary Cancer • Gynecologic Cancers • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Thoracic Cancer

Instil Bio Reports First Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "ITIL-306 phase 1 study in UK anticipated to initiate in 2H’2023: Instil has recently received positive initial feedback from the Medicines and Healthcare products Regulatory Agency, or MHRA, on the proposed study design for the phase 1 dose escalation study of ITIL-306 in the United Kingdom, and anticipates initiating such study in the second half of 2023 following anticipated Clinical Trial Application, or CTA, clearance from the MHRA. Instil expects to report initial clinical data from the ITIL-306 program in 2024."

New P1 trial • P1 data • Oncology

Instil Bio Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "ITIL-306 phase 1 study in UK anticipated to initiate in 2H'2023: Instil anticipates initiating a phase 1 study of ITIL-306 in the United Kingdom in the second half of 2023 following anticipated Clinical Trial Application, or CTA, clearance from the Medicines and Healthcare products Regulatory Agency, or MHRA. Instil anticipates initial clinical data from the ITIL-306 program in 2024."

New P1 trial • P1 data • Oncology

Anti-folate receptor alpha (FRα) CoStimulatory Antigen Receptor (CoStAR) improves T-cell function across physiologically relevant ranges of FRα expression and T-cell receptor (TCR) affinities (SITC 2022) - P1a/1b | "Further, CoStAR improved T-cell function at low FRa expression levels, supporting the evaluation of ITIL-306 activity across multiple tumors, including those with low FRα expression. These results are being explored in a first-in-human clinical study with ITIL-306 ( NCT05397093 )."

IO biomarker • Oncology • FOLR1 • HLA-A • IFNG • TNFA

ITIL-306 in Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=51 | Active, not recruiting | Sponsor: Instil Bio | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • ALK • BRCA • EGFR • KRAS

Instil Bio Announces Resumption of Clinical Trial of CoStAR-TIL Candidate ITIL-306 in Lung, Ovarian, and Renal Cancer (GlobeNewswire) - "Instil Bio...announced the resumption of its Phase 1 clinical trial of ITIL-306 for the treatment of non-small cell lung cancer (NSCLC), ovarian cancer, and renal cell carcinoma (RCC). With the resumption of the ITIL-306 Phase 1 study, the Company expects to release initial safety, translational, and efficacy data from dose escalation cohorts at a medical conference in 2023. The trial was resumed after the implementation of additional quality safeguards designed to further protect the manufacturing process from potential contaminants."

P1 data • Trial status • Genito-urinary Cancer • Gynecologic Cancers • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Instil Bio Announces Prioritization of Genetically Engineered CoStAR-TIL Program with ITIL-306 in Advanced Solid Tumors and Reduction in Workforce (GlobeNewswire) - "Instil Bio, Inc...announced a reprioritization of its clinical programs to focus on development of its CoStAR-TIL product candidates....Instil’s lead CoStAR-TIL program, ITIL-306, is in a Phase 1 dose escalation trial in non-small cell lung cancer ('NSCLC'), ovarian cancer, and renal cell carcinoma, with the first patient dosed earlier this year. The Company expects to report data from the dose escalation cohorts of the Phase 1 ITIL-306 study in 2023....Instil is undertaking a reduction in its U.S. workforce of approximately 60% to re-align its operating model from a registration-focused company to a development-stage company."

Commercial • P1 data • Pipeline update • Genito-urinary Cancer • Gynecologic Cancers • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

ITIL-306-201: A multicenter, first-in-human phase 1a/1b study of ITIL-306, an engineered autologous tumor-infiltrating lymphocyte (TIL) cell therapy product, in adults with advanced solid tumor (SITC 2022) - P1a/1b | "Key exploratory endpoints include association of biomarkers with response (eg, tumor FRα expression) and characterization of ITIL-306 activation, trafficking, persistence, and phenotype. The study is open ( NCT05397093 )."

Clinical • IO biomarker • P1 data • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • FOLR1 • IL2

Instil Bio Announces Poster Presentations of CoStAR Platform at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "The company also is presenting a trial-in-progress poster summarizing the design of the ongoing Phase 1 study of ITIL-306 (Poster 776). ITIL-306-201 is a Phase 1 multicenter, single-arm, dose escalation and expansion study evaluating the safety and feasibility of ITIL-306 in adult patients with advanced epithelial ovarian cancer (EOC), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) who relapsed from or are refractory to ≥1 prior line of systemic therapy. Importantly, the Phase 1 study of ITIL-306 features a treatment regimen free of high-dose interleukin-2."

Clinical protocol • Gynecologic Cancers • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

Instil Bio Announces Poster Presentations of CoStAR Platform at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Instil Bio, Inc....announced poster presentations of pre-clinical data and trial-in-progress for the ongoing ITIL-306 Phase 1 clinical trial using the CoStimulatory Antigen Receptor (CoStAR) platform at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), to be held from November 8-12, 2022. Pre-clinical data demonstrating the activity of CoStAR across physiologically-relevant ranges of FRα expression and TCR affinity are featured in Poster 282. These data demonstrated that CoStAR amplified T-cell responses at all FRα expression levels as long as FRα was expressed, supporting the clinical exploration of ITIL-306 in multiple solid tumor types with a variety of FRα expression levels. Furthermore, CoStAR-expressing cells do not respond to FRα in the absence of TCR stimulation, underscoring the expected safety profile of the CoStAR platform."

Preclinical • Oncology • Solid Tumor

Instil Bio Announces Voluntary Pause of Enrollment in Ongoing Clinical Trials Related to Manufacturing (GlobeNewswire) - "Instil Bio, Inc...announced that it has voluntarily paused enrollment in its ongoing clinical trials of ITIL-168 and ITIL-306 and has notified regulatory authorities in the United States, Canada, and the UK. No regulatory agencies, including the FDA, have notified the Company of a clinical hold in any of its clinical trials....The voluntary pause by the Company was instituted following a recent decrease in the rate of successful manufacturing of ITIL-168, resulting in the inability to dose some patients whose individual product of ITIL-168 was not successfully manufactured....The Company has commenced an end-to-end analysis of its manufacturing processes and upon completion of this analysis, plans to take corrective actions to improve the rate of manufacturing success and resume the study....The Company intends to provide an update on the manufacturing analysis by early Q1 2023."

Trial suspension • Cutaneous Melanoma • Genito-urinary Cancer • Gynecologic Cancers • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor

"$TIL Voluntarily paused enrollment in ITIL-168 and ITIL-306 trials pending outcome of manufacturing analysis and implementation of corrective actions" (@BioStocks)

Instil Bio Announces First Patient Dosed with ITIL-306, our First Engineered TIL Therapy Using the CoStAR Platform Targeting Folate Receptor Alpha (FRα), in Non-Small Cell Lung Cancer (GlobeNewswire) - "Instil Bio, Inc...announced that the first patient has been dosed in a Phase 1 dose escalation study of ITIL-306 (NCT05397093) for the treatment of multiple solid tumors. ITIL-306 is Instil’s first genetically-engineered Costimulatory Antigen Receptor-TIL (CoStAR-TIL) therapy...Instil’s first-in-human Phase 1 study of ITIL-306 is an open-label, multicenter study in patients with non-small cell lung cancer, ovarian cancer, and renal cell carcinoma....The company anticipates reporting initial clinical data from the Phase 1 trial in 2023."

P1 data • Trial status • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

ITIL-306 in Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=51 | Recruiting | Sponsor: Instil Bio | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • ALK • BRCA • EGFR • KRAS

Antitumor activity of T cells expressing a novel anti-folate receptor alpha (FOLR1) costimulatory antigen receptor (CoStAR) in a human xenograft murine solid tumor model and implications for in-human studies. (ASCO 2022) - "When combined with TCR-specific binding, CoStAR significantly enhanced T-cell proliferation, persistence, and antitumor activity in vivo vs TCR alone, resulting in tumor control and prolonged survival. Effects were not observed with CoStAR alone, underscoring that signaling through CoStAR alone does not induce T-cell effector function. The sustained proliferation of anti-FOLR1 CoStAR T cells without exogenous IL-2 support in vitro and in vivo supports a clinical TIL regimen free of high-dose IL-2."

Preclinical • Oncology • Solid Tumor • CEACAM5 • FOLR1 • HLA-A • PD-1

ITIL-306 in Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=51 | Not yet recruiting | Sponsor: Instil Bio

New P1 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • ALK • BRCA • EGFR • KRAS

"$TIL Instil Bio Announces IND Clearance of First CoStAR-TIL program, ITIL-306, Designed to Enhance Activity in the Tumor Microenvironment https://t.co/0jgykgrjRS" (@stock_titan)

Biomarker • Tumor microenvironment • Oncology

Instil Bio Announces IND Clearance of First CoStAR-TIL program, ITIL-306, Designed to Enhance Activity in the Tumor Microenvironment (GlobeNewswire) - "Instil Bio, Inc...announced IND clearance by the U.S. Food and Drug Administration ('FDA') of ITIL-306, Instil’s first genetically-engineered Costimulatory Antigen Receptor TIL (CoStAR-TIL) therapy, as well as the presentation of supporting in vivo CoStAR data at the 2022 ASCO Annual Meeting....The poster presentation at the 2022 ASCO Annual Meeting will outline findings from studies evaluating anti-FOLR1 CoStAR T cells in vitro as well as a mouse solid tumor model in vivo. The poster presentation highlights results demonstrating enhanced T cell function and tumor control by CoStAR-modified T cells. Importantly, improved tumor control in a mouse solid tumor model occurred without exogenous IL-2 administration, supporting a clinical CoStAR-TIL regimen free of high-dose IL-2. CoStAR T cells showed limited upregulation of PD-1 after target exposure and demonstrated improved persistence in vivo."

IND • Preclinical • Oncology • Solid Tumor