LN-145-S1 / Iovance Biotherap - LARVOL DELTA

Efficacy and safety of one-time autologous tumor-infiltrating lymphocyte cell therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. (PubMed, J Immunother Cancer) - P2 | "This study demonstrated the feasibility of consistently generating sufficient TIL from HNSCC tumors. Results from this study suggest TIL cell therapy may serve as a potential treatment option for patients with HNSCC and support further development, including TIL cell therapy combined with immune checkpoint inhibitors or other agents or with other TIL products."

Journal • Tumor-infiltrating lymphocyte • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL2 • PD-L1

NCI-2018-00918: LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ Apr 2027 | Trial primary completion date: Jun 2025 ➔ Apr 2027

Platinum resistant • Trial completion date • Trial primary completion date • Breast Cancer • Carcinosarcoma • Endocrine Cancer • Giant Cell Tumor of Bone • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Osteosarcoma • Ovarian Cancer • Refractory Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • HER-2

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=178 ➔ 245

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NCI-2018-00918: LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Jun 2024 ➔ Jun 2025 | Trial completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Breast Cancer • Endocrine Cancer • Giant Cell Tumor of Bone • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Osteosarcoma • Ovarian Cancer • Refractory Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • CD27 • CD28 • CD8 • HER-2

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Trial completion date: Dec 2024 ➔ Aug 2029 | Trial primary completion date: Dec 2023 ➔ Aug 2029

Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck (clinicaltrials.gov) - P2 | N=64 | Completed | Sponsor: Iovance Biotherapeutics, Inc. | N=112 ➔ 64

Enrollment change • Metastases • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NCI-2018-00918: LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=95 ➔ 30

Enrollment change • Enrollment closed • Breast Cancer • Endocrine Cancer • Giant Cell Tumor of Bone • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Osteosarcoma • Ovarian Cancer • Refractory Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • HER-2

NCI-2018-00918: LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial primary completion date • Breast Cancer • Endocrine Cancer • Giant Cell Tumor of Bone • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Osteosarcoma • Ovarian Cancer • Refractory Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • HER-2

Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck (clinicaltrials.gov) - P2 | N=112 | Completed | Sponsor: Iovance Biotherapeutics, Inc. | Trial primary completion date: Mar 2022 ➔ Aug 2022

Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck (clinicaltrials.gov) - P2 | N=112 | Completed | Sponsor: Iovance Biotherapeutics, Inc. | Active, not recruiting ➔ Completed | N=55 ➔ 112 | Trial primary completion date: Jun 2021 ➔ Mar 2022

Enrollment change • Trial completion • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=135 ➔ 178

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] Phase II, multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN 144/LN-145/LN-145-S1) in patients with solid tumours (ELCC 2021) - P1/2, P2 | "Lifileucel (LN-144), has shown efficacy with durable responses in advanced melanoma (Mel) (Sarnaik et al., ASCO 2020), metastatic cervical cancer (Jazaeri et al., ASCO 2019), and LN-145 + pembrolizumab in HNSCC (Jimeno et al., SITC 2020)...Cohort 3C patients receive a dose of ipilimumab and nivolumab prior to tumor harvest, with nivolumab continuing Q4W for up to 2 years, or until progression or unacceptable toxicity...The primary endpoint: ORR per RECIST v1.1. Secondary endpoints: safety, CR rate, DOR, DCR, PFS, and OS."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • IL2 • PD-1

[VIRTUAL] A Phase 2, multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN 144/LN-145/LN-145-S1) in patients with solid tumors (AACR 2021) - P2 | "Lifileucel (LN-144), has shown efficacy with durable responses in advanced melanoma (Mel) (Sarnaik et al., ASCO 2020), metastatic cervical cancer (Jazaeri et al., ASCO 2019), and LN-145 + pembrolizumab in HNSCC (Jimeno et al., SITC 2020)...Cohort 3C patients receive a dose of ipilimumab and nivolumab prior to tumor harvest, with nivolumab continuing Q4W for up to 2 years, or until progression or unacceptable toxicity...The primary endpoint: ORR per RECIST v1.1. Secondary endpoints: safety, CR rate, DOR, DCR, PFS, and OS."

Clinical • P2 data • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2 • PD-1

[VIRTUAL] Phase 2, Study of Iovance Autologous Tumor Infiltrating Lymphocytes (Lifileucel, LN - 144, LN - 145, LN - 145 - S1) In Patients With Solid Tumors (IASLC-WCLC 2021) - P2 | "Secondary endpoints: safety, CR rate, DOR, DCR, PFS, and OS. Table 1: IOV-COM-202 Study Design COHORT PATIENT POPULATION SAMPLE SIZE TREATMENT REGIMEN 1A Melanoma: PD-1/PD-L1 naive N = 12 Lifileucel + pembrolizumab 1B Melanoma: ≥ 1 prior systemic therapy(ies) N = up to 27 LN-145-S1 as single agent 1C Melanoma: ≥ 1 prior systemic therapy(ies) N = up to 27 LN-144 Gen 3 as single agent 2A HNSCC: PD-1/PD-L1 naive N = 19 LN-145 + pembrolizumab 3A NSCLC: PD-1/PD-L1 naive N = 12 LN-145 + pembrolizumab 3B NSCLC: ≥ 1 prior systemic therapy(ies) N = 12 LN-145 as single agent 3C NSCLC: 1 prior systemic therapy N = up to 26 LN-145 + ipilimumab + nivolumab"

Clinical • P2 data • Cervical Cancer • Head and Neck Cancer • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-1 • PD-L1

Iovance Biotherapeutics to Present Clinical Data for Tumor Infiltrating Lymphocyte (TIL) Cell Therapies Across Multiple Solid Tumors and Treatment Settings at the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting (GlobeNewswire) - "Iovance Biotherapeutics, Inc...announced oral and poster presentations of clinical and non-clinical data for tumor infiltrating lymphocyte (TIL) cell therapies in multiple solid tumors will be presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)....Title: Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancers"

Clinical • P2 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma

Iovance Alliance: LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas (clinicaltrials.gov) - P2; N=95; Recruiting; Sponsor: M.D. Anderson Cancer Center; Trial completion date: Dec 2022 ➔ Jun 2024; Trial primary completion date: Dec 2021 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Endocrine Cancer • Giant Cell Tumor of Bone • Immunology • Oncology • Osteosarcoma • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

Iovance Biotherapeutics to Present Updated Clinical Data for Tumor Infiltrating Lymphocyte (TIL) Therapy Lifileucel in Advanced Melanoma at American Association for Cancer Research (AACR) 2021 Annual Meeting (GlobeNewswire) - "Iovance Biotherapeutics...announced that long-term interim data from Cohort 2 in the C-144-01 clinical study (NCT02360579) in advanced melanoma has been accepted as an oral presentation in a Clinical Trials Plenary Session at the upcoming American Association for Cancer Research (AACR) 2021 Annual Meeting...In addition to the oral presentation, three Iovance poster presentations at AACR will highlight the design of clinical trials in progress in solid tumors and chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). These posters are intended to educate physicians about study design and will not include clinical data."

Clinical protocol • P2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Solid Tumor

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2; N=75; Recruiting; Sponsor: Iovance Biotherapeutics, Inc.; N=48 ➔ 75

Clinical • Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • ALK • EGFR

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2; N=135; Recruiting; Sponsor: Iovance Biotherapeutics, Inc.; N=75 ➔ 135

Clinical • Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2; N=48; Recruiting; Sponsor: Iovance Biotherapeutics, Inc.; N=36 ➔ 48

Clinical • Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • ALK • EGFR

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2; N=36; Not yet recruiting; Sponsor: Iovance Biotherapeutics, Inc.

Clinical • New P2 trial • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2; N=36; Recruiting; Sponsor: Iovance Biotherapeutics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • ALK • EGFR