ISA101 / ISA Pharma - LARVOL DELTA

HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: Dan Zandberg | Recruiting ➔ Active, not recruiting | N=50 ➔ 18 | Trial completion date: Jun 2027 ➔ Jun 2026 | Trial primary completion date: Jun 2027 ➔ Jun 2025

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

Cemiplimab and ISA101b Vaccine in Adult Participants With Recurrent/Metastatic Human Papillomavirus (HPV)16 Cervical Cancer Who Have Experienced Disease Progression After First Line Chemotherapy (clinicaltrials.gov) - P2 | N=113 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ May 2024

Trial completion • Trial completion date • Cervical Cancer • Oncology • Solid Tumor

Final results of a phase II study of peltopepimut-S and cemiplimab in patients with relapsed/metastatic HPV16+ oropharyngeal cancer that progressed with prior anti-PD-1 therapy (ESMO 2024) - P2 | "Legal entity responsible for the study: ISA Therapeutics B.V. Background: Peltopepimut-S (ISA101b) is a synthetic long peptides-based therapeutic vaccine targeting the human papillomavirus type 16 (HPV16) that induces specific expansion of both CD4+ helper and CD8+ cytotoxic T-cells against HPV16 E6/E7 oncoproteins. The combination of peltopepimut-S and cemiplimab was well tolerated, and resulted a CBR of 56.3% and mOS of 11.3 months in patients with relapsed/metastatic HPV16+ oropharyngeal cancer that progressed on or soon after anti-PD1 therapy."

Clinical • Metastases • P2 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • CD4 • CD8

Results of a randomized, double-blind, placebo-controlled, phase 2 study (OpcemISA) of the combination of ISA101b and cemiplimab versus cemiplimab for recurrent/metastatic (R/M) HPV16-positive oropharyngeal cancer (OPC). (ASCO 2024) - P2 | "Whereas there was no advantage of the addition of ISA101b to cemiplimab regarding ORR on the overall population, in patients with CPS ≥20 ISA101b significantly improved the ORR. Median OS was better in patients with CPS ≥20 who completed a full course of ISA101b. In contrast, patients with lower CPS did not benefit."

Clinical • Metastases • P2 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • CD4 • CD8

Combination of cemiplimab and ISA101b vaccine for the treatment of recurrent/metastatic HPV16 cervical cancer. (ASCO 2024) - P2 | "Results from this phase 2 study of cemiplimab + ISA101b in patients with recurrent HPV16 cervical cancer show clinical benefit, especially in patients with high PD-L1 expression, and no unexpected safety signals, supporting further research."

IO biomarker • Metastases • Anemia • Cervical Cancer • Hematological Disorders • Oncology • Solid Tumor

ProcemISA: A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC (clinicaltrials.gov) - P2 | N=65 | Active, not recruiting | Sponsor: ISA Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2023 ➔ Jun 2024

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

OpcemISA: A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC (clinicaltrials.gov) - P2 | N=194 | Active, not recruiting | Sponsor: ISA Pharmaceuticals | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

ISA Pharmaceuticals reports highlights of randomized Phase 2 cancer vaccine trial in head & neck cancer (PRNewswire) - P2 | N=194 | NCT03669718 | Sponsor: ISA Pharmaceuticals | "ISA Pharmaceuticals B.V...announced positive anti-tumor response data with ISA101b, an HPV16 directed therapeutic cancer vaccine given in combination with Libtayo^®, an anti-PD1 checkpoint inhibitor (CPI). The data were generated in the OpcemISA trial, a large scale randomized double blind study that is ongoing in patients with advanced oropharyngeal cancer (OPC), a type of head and neck cancer...Whereas the addition of ISA101b to the CPI led to a doubling of the ORR (from 26.7% to 51.9%) in a large subgroup of patients, the study as a whole did not meet this primary endpoint. Patients in the aforementioned subgroup, predefined based on a validated biomarker, also showed a clear overall survival benefit compared to the placebo arm. ISA101b was well tolerated."

P2 data • Head and Neck Cancer • Oropharyngeal Cancer

Cemiplimab and ISA101b Vaccine in Adult Participants With Recurrent/Metastatic Human Papillomavirus (HPV)16 Cervical Cancer Who Have Experienced Disease Progression After First Line Chemotherapy (clinicaltrials.gov) - P2 | N=113 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Trial primary completion date: Oct 2024 ➔ May 2023

Metastases • Trial primary completion date • Cervical Cancer • Oncology • Solid Tumor

HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Dan Zandberg | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Jun 2027

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

Phase 2 study of ISA101b (peltopepimut-S) and cemiplimab in patients with advanced HPV16+ oropharyngeal cancer who failed anti-PD1 therapy. (ASCO 2023) - P2 | "Previously we showed that ISA101 with nivolumab achieved a higher response rate compared to immune checkpoint inhibitor (ICI) alone in trials for patients with recurrent/metastatic (R/M) HPV16+ oropharyngeal cancer (OPC)1,2. This treatment appears promising for HPV16+ OPC patients who failed prior anti-PD-1 ICI therapy, with an ORR of 11.5% and a CBR of 61.5%. In this small, ongoing study the combination of cemiplimab and ISA101b was well tolerated with a safety profile resembling anti-PD-1 monotherapy. This is the first study of the combination of ISA101b and cemiplimab in 2nd/3rd line R/M anti-PD-1 refractory OPC patients."

Clinical • Metastases • P2 data • Dermatology • Head and Neck Cancer • Immune Modulation • Immunology • Oncology • Oropharyngeal Cancer • Solid Tumor

The combination of ISA101b and Libtayo shows promising results in patients whose head and neck cancer progressed on anti-PD1 therapy (PRNewswire) - P2 | N=86 | NCT04398524 | Sponsor: ISA Pharmaceuticals | "ISA Pharmaceuticals B.V...presented the first clinical data of the combination of ISA101b (peltopepimut-S) and Regeneron's anti-PD-1 Libtayo® (cemiplimab) at the ASCO annual meeting in Chicago....The combination of ISA101b and cemiplimab in these patients resulted in an overall response rate (ORR) of 15.4%, as per investigator assessment. Long term (≥6 months) disease stabilization was achieved in 26.9% of all patients. The combination of cemiplimab and ISA101b was generally well tolerated with a safety profile resembling that of anti-PD-1 monotherapy."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

ISA Pharmaceuticals to Present First Clinical Trial Data from the Phase II Study of ISA101b and Libtayo (cemiplimab) Combination in Head and Neck Cancer at the ASCO Annual Meeting 2023 (PRNewswire) - "ISA Pharmaceuticals B.V...announces that it will present the first clinical data of the combination of ISA101b and Regeneron's PD-1 inhibitor Libtayo® (cemiplimab) in patients with recurrent metastatic Human Papilloma Virus type 16 (HPV16) induced head and neck cancers who progressed on pembrolizumab or nivolumab. Patients with recurrent and/or metastatic HPV16 positive OPC who experienced disease progression during or within 6 months after prior anti-PD1 therapy were to be treated until disease progression or withdrawal. Patients that never responded to prior treatment were also included....Recruitment in this study is ongoing; results of the complete trial will become available mid-2024."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor

ProcemISA: A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: ISA Pharmaceuticals | Trial primary completion date: Mar 2023 ➔ Dec 2023

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

Nivolumab and ISA 101 HPV vaccine in incurable HPV-16+ cancer (ESMO 2017) - P2; "...12 pts (50%) had prior cetuximab...The primary endpoint was met and ORR of 36% in OPC pts compares favorably to 16% for nivolumab monotherapy in p16+ OPC pts in Checkmate 141 (Ferris RL et al N Engl J Med 2016; 375:1856). These data suggest that the efficacy of vaccine-induced T cells can be augmented by anti-PD-1 therapy, mitigating the influence of an immunosuppressive microenvironment. Our findings merit confirmation in a larger randomized trial."

Clinical • Cervical Cancer • Head and Neck Cancer

Combination immunotherapy with synthetic long peptides and chemotherapy or PD-1 blocker for cancers caused by human papilloma virus type 16. (PubMed, Semin Immunopathol) - "In patients with late-stage recurrent or metastatic HPV16+ cancers, we have therefore combined treatment with the SLP vaccine, called ISA101b, with either standard-of-care chemotherapy or with immune checkpoint inhibition with anti-PD-1 monoclonal antibody. In this trial, the clinical overall response rate (ORR) in 22 patients was 36%, twice the ORR in the nivolumab registration trial for this category of patients, and 2/22 patients had a complete clinical response that is ongoing after 4 1/2 years. Other promising strategies for late-stage cancer recipients are the infusion of expanded tumor-infiltrating lymphocytes or the infusion of T cell receptor transduced T cells, both directed against HPV16."

Journal • Review • Head and Neck Cancer • Immune Modulation • Oncology • Oropharyngeal Cancer • Solid Tumor • IFNG

OpcemISA: A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC (clinicaltrials.gov) - P2 | N=194 | Active, not recruiting | Sponsor: ISA Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2022 ➔ Sep 2023

Enrollment closed • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Cemiplimab and ISA101b Vaccine in Adult Participants With Recurrent/Metastatic Human Papillomavirus (HPV)16 Cervical Cancer Who Have Experienced Disease Progression After First Line Chemotherapy (clinicaltrials.gov) - P2 | N=113 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Cervical Cancer • Oncology • Solid Tumor

Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; Closed the trial for infeasibility due to slow accrual

Trial termination • Head and Neck Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

ISA Pharmaceuticals Completes Enrolment in Randomized Double Blind Phase 2 Clinical Trial of ISA101b in HPV16 induced Oropharyngeal Cancer (PRNewswire) - "ISA Pharmaceuticals...is delighted to announce that it has completed enrolment in its Phase 2 clinical trial named OpcemISA. The OpcemISA trial has enrolled 194 patients and is a large randomized, double blind, placebo-controlled Phase 2 clinical trial. The trial will evaluate the efficacy and safety of the addition of ISA101b to checkpoint inhibitor therapy in patients with metastatic/advanced 1st and 2nd line HPV16 positive OPC....'We look forward to presenting top line interim data from this trial in the third quarter of next year'."

Enrollment closed • P2 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor

A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: ISA Pharmaceuticals | Trial primary completion date: Dec 2022 ➔ Mar 2023

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

Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV-16 positive (pre-)malignant lesions. (PubMed, J Immunother Cancer) - P1 | "Amplivant-conjugated SLPs can safely be used as an intradermal therapeutic vaccine to induce robust HPV16-specific T cell immunity in patients previously treated for HPV16 positive (pre-) malignancies. Increased vaccine dose was associated with a higher number of mild adverse events and with stronger systemic T cell immunity."

Journal • Dermatitis • Immunology • Inflammation • Oncology • TLR2

A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC (clinicaltrials.gov) - P2 | N=194 | Recruiting | Sponsor: ISA Pharmaceuticals | Trial completion date: Nov 2022 ➔ Dec 2024 | Trial primary completion date: Jun 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC (clinicaltrials.gov) - P2; N=86; Recruiting; Sponsor: ISA Pharmaceuticals; Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Dan Zandberg | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

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