ADXS-PSA / Ayala Pharma - LARVOL DELTA

KEYNOTE-046: ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1/2 | N=50 | Completed | Sponsor: Advaxis, Inc. | Unknown status ➔ Completed

Combination therapy • Metastases • Trial completion • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel. (ASCO-GU 2020) - P1/2; "Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557. Research Funding: None."

Clinical • Combination therapy • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK3

KEYNOTE-046: ADXS-PSA plus pembrolizumab (pembro) in metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2018) - P1/2; "... At entry, PA and PB pts were similar in age (~70 yrs), Gleason score (~8.3) and prior abirateroneuse. PB pts had higher median BL PSA (40.6 v 20.8 ng/ml), and more prior enzalutamide (53 v 26%) and chemotherapy (49 v 36%) use v PA... In this population of heavily pretreated mCRPC pts ADXS-PSA + pembro had a manageable safety profile and showed promising activity compared to monotherapy. These preliminary data warrant further study."

Prostate Cancer

KEYNOTE-046: Effects of ADXS-PSA with or without pembrolizumab on survival and antigen spreading in metastatic, castration-resistant prostate cancer patients (AACR 2019) - P1/2; "Updates on OS and T cell reactivity to PSA and to other prostate cancer antigens (i.e., prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and prostein) are herein presented for PA and PB pts. At entry, PA and PB pts were ~70 yrs with a Gleason score >8 and the majority had received prior abiraterone and/or enzalutamide. ADXS-PSA ± pembro elicited a broad antitumor T cell response in all mCRPC pts tested but only ADXS-PSA + pembro reduced PSA ≥50% from BL and prolonged OS in these select pts. Clinical trial information: NCT02325557."

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ADXS31-142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study. (PubMed, Oncologist) - P1/2 | "Combining ADXS31-142 with pembrolizumab was safe and well tolerated. The observed OS in mCRPC warrants further testing of this combination."

Journal • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Advaxis Announces Publication of ADXS-PSA Data in The Oncologist (GlobeNewswire) - P1/2 | N=51 | Keynote-46 (NCT02325557) | Sponsor: Advaxis, Inc | "The median overall survival (OS) in 13 patients treated with ADXS-PSA alone was 7.8 months (95%CI: 4.4-18.5) with progression free survival (PFS) of 2.2 months (95%CI: 0.8–7.4). The median OS on ADXS-PSA combined with KEYTRUDA® was 33.7 months (95%CI: 15.4-NR), while median PFS was 5.4 months (95%CI: 2.3–7.9; n=37). 56.8% (21/37) of patients on combination therapy and 30.8% (4/13) on monotherapy showed stable disease. Robust response was also observed with the combination therapy in patients with prior docetaxel treatment and visceral metastasis. In addition, patients in the combination arm who had prior docetaxel treatment (n=20; 17 of whom had also received 1 or 2 next generation hormonal agent (NGHA) therapies) had an OS of 16.0 months (95%CI: 6.4-34.6), while patients with prior visceral metastasis (n=11; 10 of whom had prior docetaxel and 9 whom had received 1-2 prior NGHA therapies) ..".

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer

KEYNOTE-046: ADXS-PSA plus pembrolizumab (pembro) in metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2018) - P1/2; "... At entry, PA and PB pts were similar in age (~70 yrs), Gleason score (~8.3) and prior abirateroneuse. PB pts had higher median BL PSA (40.6 v 20.8 ng/ml), and more prior enzalutamide (53 v 26%) and chemotherapy (49 v 36%) use v PA... In this population of heavily pretreated mCRPC pts ADXS-PSA + pembro had a manageable safety profile and showed promising activity compared to monotherapy. These preliminary data warrant further study."

Prostate Cancer

KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel. (ASCO-GU 2020) - P1/2; "Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557. Research Funding: None."

Clinical • Combination therapy • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK3

Advaxis begins phase 3 study of AXAL for advanced cervical cancer - "Advaxis has begun its Phase 3 clinical trial evaluating axalimogene filolisbac, or AXAL, administered in the adjuvant setting following chemotherapy and radiation in women with high-risk, locally advanced cervical cancer....Advaxis also announced the commencement of Part B of its Phase 1/2 clinical trial (KEYNOTE-046, NCT02325557) evaluating ADXS-PSA, in combination with Keytruda (pembrolizumab) in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC)."

Anticipated new P1/2 trial • New P3 trial • Cervical Cancer • Oncology • Prostate Cancer

Advaxis appoints Mayo Pujols Vice President, Manufacturing (Advaxis, Inc Press Release) - "Advaxis expects to initiate four new clinical trials in 2015 involving its Lm-LLO immunotherapy platform...The planned clinical trial will evaluate the safety and efficacy of ADXS-PSA as monotherapy and in combination with pembrolizumab in a Phase 1/2 study of patients with previously treated metastatic, castration-resistant prostate cancer."

Anticipated new P1/2 trial • Prostate Cancer

Advaxis reports first quarter ended january 31, 2020 financial results and provides a pipeline update (GlobeNewswire) - "''We have started our fiscal year with encouraging positive data presented in our ADXS-PSA and ADXS-503 clinical programs...We continue to execute on our HOT off-the-shelf program in NSCLC with enrollment continuing in the combination arm of the study, Part B, and a planned initiation of Part C which will move combination therapy to a first-line setting, later this year. We are also planning to move an additional HOT construct, ADXS-504, for prostate cancer, into the clinic later this year'....'We are currently evaluating next steps for our ADXS-PSA program based on the promising increases in median overall survival observed in combination with KEYTRUDA.'"

Enrollment status • New trial • Trial status

ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Patients With Prostate Cancer - KEYNOTE-046 (clinicaltrials.gov) - P1/2; N=51; Active, not recruiting; Sponsor: Advaxis, Inc.; Trial completion date: Dec 2019 ➔ Dec 2021; Trial primary completion date: Apr 2019 ➔ Jan 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date

Advaxis announces updated survival data in phase 1/2 ADXS-PSA trial at the ASCO Genitourinary Cancers Symposium (GlobeNewswire) - P1/2, N=51; KEYNOTE-046 (NCT02325557); Sponsor: Advaxis, Inc; "Advaxis, Inc...announced updated results from the combination arm of KEYNOTE-46 (Part B), the Company’s ongoing Phase 1/2 study investigating ADXS-PSA with KEYTRUDA^® (pembrolizumab) in patients with metastatic, castrate-resistant prostate cancer (mCRPC) at the ASCO Genitourinary Cancers Symposium in San Francisco, California...Median overall survival (95% CI) of 33.7 months (15.4-NR) for patients treated with ADXS-PSA in combination with KEYTRUDA^® (n=37)....Median overall survival (95% CI) of 16.0 months (6.4-34.6) for patients with prior docetaxel (n=20)"

P1/2 data

Data on Advaxis’ clinical programs to be presented at upcoming medical meetings (GlobeNewswire, Advaxis, Inc.) - "Advaxis, Inc...today announced the following upcoming presentations at medical meetings: Title: 'KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel'; A Phase 1 Study of ADXS-503 Alone and in Combination with Pembrolizumab in Subjects with Metastatic Squamous or Non-Squamous Non-Small Cell Lung Cancer."

P1 data • P1/2 data

Advaxis announces updated prolonged survival data in phase 1/2 ADXS-PSA trial (Advaxis, Inc Press Release) - P1/2, N=51; KEYNOTE-046 (NCT02325557); Sponsor: Advaxis, Inc; “Advaxis, Inc….announced updated median overall survival data from its Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC)…. At the final data cutoff of September 16, 2019, median overall survival for 37 patients in the combination arm was 33.6 months (95% CI, range 15.4-33.6 months)….These new data, along with additional details from this final predetermined look at the trial results, will be presented at an upcoming medical conference….The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and KEYTRUDA® has appeared to be well-tolerated, to date, with no additive toxicity observed.”

P1/2 data

Advaxis reports fiscal third quarter 2019 financial results and provides pipeline update (Businesswire) - P1, N=48; NCT03265080; Sponsor: Advaxis, Inc; P1/2, N=51; KEYNOTE-046 (NCT02325557); Sponsor: Advaxis, Inc; "Presented early immune response and clinical data from the Phase 1 ADXS-NEO study...Preliminary direct ELISpot data showed that CD8+ T cell reactivity was generated in >90% of neoantigen pools from four patients so far treated (i.e., 1X 109 colony forming units (CFU) (n=2) and 1X108 CFU (n=2)) as well as antigen spreading...Findings from the first poster, 'Effects of ADXS-PSA With or Without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients (Results from KEYNOTE-046),' showed prolonged survival in prostate cancer patients with advanced and microsatellite-stable (MSS) disease..."

P1 data • P1/2 data

ADXS-PSA in combination with Keytruda prolonged survival in metastatic castration-resistant prostate cancer (Businesswire) - P1/2, N=51; KEYNOTE-046 (NCT02325557); Sponsor: Advaxis; “Advaxis, Inc…announced updated data from the Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC)....The combination of ADXS-PSA and pembrolizumab has been well-tolerated, to date, with no additive toxicity observed. Median overall survival was 21.1 months at data cutoff (February 1, 2019) (95% CI, range 16.0 months to not-yet-reached) in this dataset of 37 patients. Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects.”

P1/2 data

Advaxis announces presentations of ADXS-NEO and ADXS-PSA data at upcoming American Association for Cancer Research Annual Meeting (Businesswire) - P1/2, N=51; KEYNOTE-046 (NCT02325557); Sponsor: Advaxis; "Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, announced today two poster presentations at the upcoming American Association for Cancer Research (AACR) Annual Meeting being held March 29 – April 3, 2019 in Atlanta, Georgia."

P1/2 data