Lovaxin C (axalimogene filolisbac) / Ayala Pharma - LARVOL DELTA

Axalimogene Filolisbac (ADXS11-001) High Dose in Women With Human Papillomavirus (HPV) + Cervical Cancer (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Advaxis, Inc. | Phase classification: P1/2 ➔ P1 | N=25 ➔ 12

Enrollment change • Phase classification • Cervical Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

A Study of Pemetrexed Maintenance With or Without ADXS11-001 Immunotherapy in Patients With Human Papillomavirus Positive (HPV+), NSCLC Following First-Line Induction Chemotherapy (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Advaxis, Inc. | N=124 ➔ 0 | Unknown status ➔ Withdrawn

Enrollment change • Trial withdrawal • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of ADXS11-001 or MEDI4736 Alone or Combination In Cervical or Human Papillomavirus (HPV)+ Head & Neck Cancer (clinicaltrials.gov) - P1/2 | N=75 | Terminated | Sponsor: Advaxis, Inc. | Unknown status ➔ Terminated

Metastases • Trial termination • Cervical Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

AIM2CERV: Study of ADXS11-001 in Participants With High Risk Locally Advanced Cervical Cancer (clinicaltrials.gov) - P3 | N=110 | Terminated | Sponsor: Advaxis, Inc. | N=450 ➔ 110 | Active, not recruiting ➔ Terminated

Enrollment change • Metastases • Trial termination • Cervical Cancer • Oncology • Solid Tumor

Phase II study of durvalumab alone or in combination with ADXS11-001 (AXAL) in recurrent/persistent or metastatic cervical cancer (SGO 2020) - "The combination of durvalumab + ADXS11-001 appears to be safe and tolerable but requires close monitoring. The ORR was similar across arms, and the PFS in the durvalumab arm was numerically higher than that observed with durvalumab + ADXS11-001. Two objective responses were previously reported in subjects in part A, dose escalation of the study (ADXS11-001 at 1 × 109 CFU + MEDI 3 mg/kg, n = 4), including a complete response."

Combination therapy • P2 data • Cervical Cancer • Endocrine Disorders • Fatigue • Gynecologic Cancers • Head and Neck Cancer • Hematological Disorders • Hypotension • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Oncology • Pain • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • PD-L1

ADXS11-001 Lm-LLO Immunotherapy, Mitomycin, 5-fluorouracil (5-FU) and Intensity-modulated radiation therapy (IMRT) for Anal Cancer. (ASCO 2017) - P1/2; "ADXS11-001 can be safely administered with CRT for anal cancer. Promising PFS was observed in patients with locally advanced disease."

Anal Carcinoma • Biosimilar • Heart Failure • Pain

P2 study of ADXS11-001 Immunotherapy in patients with persistent/recurrent, surgically unresectable locoregional, or metastatic squamous cell anal cancer (ESMO 2017) - P2; "ADXS monotherapy showed promising activity and met the predefined 6-month PFS rate. Treatment was well-tolerated with mostly grade 1-2 infusion related AEs that resolved successfully with standard care. Further investigation is ongoing in this population."

Adverse events • Anal Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Andrew Sikora | Active, not recruiting ➔ Completed

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

Phase II study of durvalumab alone or in combination with ADXS11-001 (AXAL) in recurrent/persistent or metastatic cervical cancer (SGO 2020) - "The combination of durvalumab + ADXS11-001 appears to be safe and tolerable but requires close monitoring. The ORR was similar across arms, and the PFS in the durvalumab arm was numerically higher than that observed with durvalumab + ADXS11-001. Two objective responses were previously reported in subjects in part A, dose escalation of the study (ADXS11-001 at 1 × 109 CFU + MEDI 3 mg/kg, n = 4), including a complete response."

Combination therapy • P2 data • Cervical Cancer • Endocrine Disorders • Fatigue • Gynecologic Cancers • Head and Neck Cancer • Hematological Disorders • Hypotension • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Oncology • Pain • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • PD-L1

Prediction of the influence of vertical whole-body vibration on biomechanics of spinal segments after lumbar interbody fusion surgery. (PubMed, Clin Biomech (Bristol, Avon)) - "Although whole-body vibration is still more dangerous for the lumbar spine after interbody fusion surgery than static loading, the sensitivity of adjacent segment in postsurgical spine to vibration loading is decreased compared with healthy spine, especially when reaching to bony fusion."

Journal

ADXS11-001 LM-LLO as specific immunotherapy in cervical cancer. (PubMed, Hum Vaccin Immunother) - "These HPV-specific CTLs destroy HPV infected cells. ADXS11-001 has demonstrated safety results in phase I-II studies in women with cervical cancer and is being assessed in clinical trials in patients with HPV-positive anal canal and head and neck cancers."

Journal • Cervical Cancer • Head and Neck Cancer • Infectious Disease • Oncology • Solid Tumor

Changes in local and peripheral T cell diversity after HPV E7 antigen-expressing Listeria-based immunotherapy (ADXS11-001) prior to robotic surgery for HPV-positive oropharyngeal cancer (AACR 2018) - "Clonal expansion and diversification of PBMCs and tumor TILs post-treatment were determined via T cell receptor (TCR) DNA sequencing and correlated to HPV antigen specific immune responses determined by ELISPOT as well as tumor immune profile determined by quantitative immunofluorescence. Our results demonstrate that immunomodulatory effects of ADXS11-001 on the local and peripheral immune response vary among patients, with 2/8 treated patients demonstrating evidence of an integrated adaptive immune response in blood and tumor, consistent with selective clonal expansion in the context of a vaccine-induced anti-tumor T cell response. Profiling of additional patients will permit more detailed analysis of ADXS11-induced immune modulation and impact on TCR diversity."

IO Biomarker • PD(L)-1 Biomarker • Head and Neck Cancer

Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study. (PubMed, Gynecol Oncol) - P2 | "At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma."

Journal • P2 data • Cervical Cancer • Fatigue • Gynecologic Cancers • Hematological Disorders • Oncology • Solid Tumor

[VIRTUAL] Phase II study of durvalumab alone or in combination with ADXS11-001 (AXAL) in recurrent/persistent or metastatic cervical cancer (SGO-I 2020) - "The combination of durvalumab + ADXS11-001 appears to be safe and tolerable but requires close monitoring. The ORR was similar across arms, and the PFS in the durvalumab arm was numerically higher than that observed with durvalumab + ADXS11-001. Two objective responses were previously reported in subjects in part A, dose escalation of the study (ADXS11-001 at 1 × 109 CFU + MEDI 3 mg/kg, n = 4), including a complete response."

Combination therapy • P2 data • Cervical Cancer • Endocrine Disorders • Fatigue • Gynecologic Cancers • Head and Neck Cancer • Hematological Disorders • Hypotension • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Oncology • Pain • Respiratory Diseases • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • PD-L1

A phase II evaluation of ADXS11-001 in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix Safety lead in performed by Phase I subcommittee - completed. ASCO 2016 (NRG 2020) - No abstract available

Clinical • P1 data • P2 data • Cervical Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer (clinicaltrials.gov) - P2; N=67; Active, not recruiting; Sponsor: Gynecologic Oncology Group; N=54 ➔ 67

Enrollment change • Biosimilar • Gynecologic Cancers • Non-Hodgkin’s Lymphoma

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer (clinicaltrials.gov) - P2; N=67; Suspended; Sponsor: Gynecologic Oncology Group; Active, not recruiting ➔ Suspended

Trial suspension • Biosimilar • Oncology

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer (clinicaltrials.gov) - P2; N=67; Recruiting; Sponsor: Gynecologic Oncology Group; Active, not recruiting -> Recruiting

Enrollment open • Biosimilar • Immunology • Oncology

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer (clinicaltrials.gov) - P2; N=54; Active, not recruiting; Sponsor: Gynecologic Oncology Group; Suspended ➔ Active, not recruiting

Enrollment closed • Biosimilar • Gynecologic Cancers • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer (clinicaltrials.gov) - P2; N=54; Completed; Sponsor: Gynecologic Oncology Group; Active, not recruiting ➔ Completed

Clinical • Trial completion • Cervical Cancer • Oncology • Psychiatry • Solid Tumor • Squamous Cell Carcinoma

Advaxis announces FDA acceptance of its Investigational New Drug Application to commence clinical trials of ADXS-HPV in combination with MedImmune's MEDI4736 for the treatment of HPV-associated cancers (Advaxis, Inc Press Release) - "Advaxis...announced...that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to conduct a Phase 1/2 clinical study of ADXS-HPV (ADXS11-001) alone or in combination with MedImmune's investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, for the treatment of advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer. The trial is expected to begin patient enrollment in early 2015."

Anticipated new P1/2 trial • IND • Head and Neck Cancer • Oncology

Advaxis lead immunotherapy candidate continues to build recognition among industry leaders (Advaxis, Inc Press Release) - "The peer-reviewed journal Gynecologic Oncology Research and Practice (GORP) published a review article, entitled 'Mechanistic insights into ADXS11-001 human papillomavirus-associated cancer immunotherapy'...illustrating the mechanism of action of axalimogene filolisbac and the scientific validity of using Listeria monocytogenes (Lm) as an immunotherapeutic bacterial vector....Bradley J. Monk, MD...cowrote the article."

Media quote

276: A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer (clinicaltrials.gov) - P1/2; N=11; Terminated; Sponsor: Brown University; Active, not recruiting ➔ Terminated; pilot data to be used for upcoming larger trial.

Trial termination • Anal Carcinoma • Biosimilar • Gastrointestinal Cancer • Oncology • Solid Tumor

A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer. (PubMed, Oncotarget) - "However, this study did not meet either primary endpoint. ADXS11-001 may be more beneficial when administered in combination with other cytotoxic or targeted agents."

Clinical • Journal • P2 data

ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer (clinicaltrials.gov) - P2; N=15; Active, not recruiting; Sponsor: Andrew Sikora; Recruiting ➔ Active, not recruiting; N=30 ➔ 15

Clinical • Enrollment change • Enrollment closed