IOV-4001 / Iovance Biotherap - LARVOL DELTA

Recent Advances in Tumor-Infiltrating Lymphocyte Therapy for Melanoma. (PubMed, Curr Treat Options Oncol) - "We then review current clinical evidence for conventional TIL products, including lifileucel, TM001, LM103, HS-IT101, and GC101, highlighting their efficacy and safety profiles...In addition, advances in genetically engineered TILs, such as OBX-115, KSQ-001EX, and IOV-4001, are reviewed...Challenges and future directions of TIL therapy in melanoma are also discussed. Overall, TIL therapy constitutes a rapidly evolving and clinically potent treatment modality for melanoma."

Biomarker • IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • IL2

A phase I/II open-label study (IOV-GM1-201) of TALEN-mediated PD-1 inactivated autologous tumor-infiltrating lymphocytes (TIL; IOV-4001) in patients with advanced melanoma and NSCLC (ESMO 2022) - P1/2 | "The primary endpoints of phases 1 and 2 are safety (DLTs and AEs) and objective response rate per RECIST v1.1, respectively. Secondary endpoints include complete response rate, duration of response, disease control rate, progression-free survival, overall survival, feasibility, and additional safety."

Clinical • IO biomarker • P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

IOV-GM1-201: A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=53 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Trial completion date: Jun 2027 ➔ Sep 2029 | Trial primary completion date: Jun 2025 ➔ Sep 2027

Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Next Generation Pipeline (The Manila Times) - "An Investigational New Drug (IND) application was submitted to FDA for a Phase 1/2 basket trial of IOV-5001, a second-generation IL-12 tethered TIL therapy, to begin enrolling in 2H 2026. Cohorts include advanced colorectal cancer, triple negative and estrogen receptor low breast cancers, and other highly prevalent solid tumors...A Phase 1/2 trial, IOV-GM1-201, is enrolling using IOV-4001, a PD-1 inactivated TIL therapy, in previously treated advanced melanoma and NSCLC....A Phase 1 safety cohort using IOV-3001 is advancing through multiple dose levels in the Phase 1/2 trial of our second-generation, modified IL-2 analog for the TIL treatment regimen."

New P1/2 trial • Trial status • Colorectal Cancer • Hormone Receptor Breast Cancer • Melanoma • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Pipeline Updates (The Manila Times) - "New Data Across Several Pipeline Programs Anticipated Throughout 2026...The Phase 3 TILVANCE-301 trial of lifileucel and pembrolizumab in frontline advanced melanoma made significant progress, with enrollment accelerating across a broad and expanding global footprint...Two of Iovance’s Phase 2 trials, IOV-END-201 and IOV-MEL-202, are investigating lifileucel in previously treated patients with advanced endometrial cancer and melanoma, respectively...A Phase 1/2 trial is investigating IOV-4001...A Phase 1/2 trial is investigating IOV-3001...An Investigational New Drug (IND) submission is planned in the first half of 2026 to begin clinical development of IOV-5001, a genetically engineered, inducible, and tethered interleukin-12 TIL therapy, in a Phase 1/2 basket trial."

Clinical data • IND • New P1/2 trial • P2 data • Trial status • Endometrial Cancer • Melanoma • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology

Pipeline Progress and Anticipated Milestones by Program: Next Generation Programs (GlobeNewswire) - "Clinical results for IOV-4001, a PD-1 inactivated TIL cell therapy, in previously treated advanced melanoma patients are anticipated in the first quarter of 2026....Dose escalation is continuing for IOV-3001, a second-generation, modified IL-2 analog for use in the TIL therapy treatment regimen....Advancement into Phase 2 development is expected in 2026."

New P2 trial • P1/2 data • Trial status • Melanoma

Next Generation TIL Pipeline (GlobeNewswire) - "PD-1 Inactivated TIL Cell Therapy (IOV-4001): Results are anticipated in the second half of 2025 from the Phase 2 efficacy portion of the IOV-GM1-201 trial in previously treated advanced melanoma...Next Generation Interleukin-2 (IL-2) for TIL Treatment Regimen (IOV-3001): Patient enrollment continues in a Phase 1/2 clinical trial, IOV-IL2-101, to investigate IOV-3001, a second-generation, modified IL-2 analog for use in the TIL therapy treatment regimen....Next Generation, Cytokine-Tethered TIL Therapy (IOV-5001): IND-enabling studies are proceeding for IOV-5001, a genetically engineered, inducible, and tethered interleukin-12 TIL cell therapy, in support of an IND in early 2026 for clinical development for multiple indications."

IND • P2 data • Trial status • Melanoma • Oncology

Trial in progress: A phase 1/2 open-label study (IOV-GM1-201) of TALEN-mediated PD-1-inactivated autologous tumor-infiltrating lymphocytes (TIL; IOV-4001) in patients with advanced melanoma and NSCLC (SITC 2022) - P1/2 | "Secondary endpoints include complete response rate, duration of response, disease control rate, progression-free survival, overall survival, feasibility, and additional safety. Trial Registration NCT05361174"

Clinical • IO biomarker • P1/2 data • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

Iovance Biotherapeutics Announces Updated Clinical Data for Lifileucel in Advanced Melanoma at Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Iovance Biotherapeutics...announced the publication of abstracts reporting...a trial in progress (TIP) for Iovance tumor-infiltrating lymphocyte (TIL) cell therapies for the upcoming Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 8-12, 2022, in Boston, MA and virtually."

Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer

Iovance Biotherapeutics Announces First Patient Dosed with PD-1 Inactivated Tumor Infiltrating Lymphocyte (TIL) Therapy (GlobeNewswire) - "Iovance Biotherapeutics, Inc...announced that the first patient was dosed, and completed the safety observation period, in the IOV-GM1-201 trial of Iovance’s genetically modified, PD-1 inactivated TIL therapy, IOV-4001. IOV-GM1-201 is a Phase 1/2, first-in-human study investigating the safety and efficacy of IOV-4001 in patients with previously treated metastatic non-small cell lung cancer (NSCLC) or advanced melanoma....IOV-GM1-201 is actively enrolling adult participants with advanced NSCLC or unresectable or metastatic melanoma."

Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Iovance Biotherapeutics to Present Clinical Data for Lifileucel Tumor Infiltrating Lymphocyte (TIL) Therapy in Advanced Melanoma at Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting (GlobeNewswire) - "Iovance Biotherapeutics, Inc...announced oral and poster presentations reporting clinical data and trial design for tumor infiltrating lymphocyte (TIL) cell therapies at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting in Boston, Massachusetts, November 8-12, 2022....Iovance will host a webcast and conference call on Thursday, November 10, 2022 at 4:30 p.m. ET to discuss the pooled analysis of Cohorts 2 and 4 of the C-144-01 study of lifileucel in advanced melanoma."

P2 data • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Iovance Biotherapeutics to Present Posters at ESMO 2022 (GlobeNewswire) - "Iovance Biotherapeutics...announced the publication of abstracts reporting clinical data and trial design for tumor infiltrating lymphocyte (TIL) cell therapies at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris, France, September 9 – 13, 2022."

Clinical protocol • P2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=53 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=53 | Not yet recruiting | Sponsor: Iovance Biotherapeutics, Inc.

New P1/2 trial • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Preclinical activity and manufacturing feasibility of genetically modified PDCD-1 knockout (KO) tumor-infiltrating lymphocyte (TIL) cell therapy (AACR 2022) - "Background: Adoptive cell therapy with autologous TIL has demonstrated an objective response rate (ORR) of 36% in the post-immune checkpoint inhibitor (ICI) setting in patients (pts) with advanced/unresectable melanoma (Sarnaik JCO 2021), while in ICI-naïve pts who received early-line combination of TIL and pembrolizumab, the ORR was 60%, with a 30% CR rate (O’Malley SITC 2021). Although effective, anti-PD-1 therapy is limited by poor penetration into the tumor, internalization, and endocytic clearance, in contrast with TIL, which overcome this inherent limitation... Anti-tumor activity of PD-1 KO TIL was superior to mock TIL suggesting that endogenous PD-1 inhibition may confer a functional advantage to the TIL over an antibody combination. PD-1 KO TIL clinical manufacturing was feasible and the TIL product quality attributes and phenotype were acceptable; importantly, lack of complete PD-1 KO may spare other PD-1-dependent in vivo cellular functions. Together,..."

IO biomarker • Preclinical • Melanoma • Oncology • Solid Tumor • PD-1 • PTPRC

Iovance Biotherapeutics’ Investigational New Drug Application (IND) Allowed to Proceed for TALEN-Edited Tumor Infiltrating Lymphocyte (TIL) in Unresectable or Metastatic Melanoma and Stage III or IV Non-Small Cell Lung Cancer (NSCLC) (GlobeNewswire) - "Iovance Biotherapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has allowed an Investigational New Drug Application (IND) to proceed for its first genetically modified TIL therapy, IOV-4001, for the treatment of unresectable or metastatic melanoma and stage III or IV NSCLC...A clinical study of IOV-4001 in patients with metastatic melanoma or stage III or IV NSCLC is expected to begin in 2022."

IND • New trial • Melanoma • Oncology