Sunday, May 8, 2016

CAVATAK - intralesional therapy derived from the coxsackievirus

Many intralesional therapies, medicine that is injected directly into a tumor, have been found to have some success in melanoma.  We have learned that, at times, they can not only kill the tumor into which they are injected, but "by-stander" tumors as well. First tried in 1975 with the BCG vaccine, things as disparate as IL2, Allovectin-7 (a DNA mixture), T-VEC/OncoVEX (derived from the herpes virus), L19, PV-10 (from the dye Rose Bengal), GM-CSF, and CAVATAK (derived from the coxsackievirus) have been used.  Additionally, some of these intralesionals have been tested combined with systemic immunotherapy.  The idea being that one could prime an immune response by injecting a tumor with an oncolytic virus, eliciting a T-cell influx, and follow with systemic immunotherapy.

Here's some background on the process:  Intralesional therapy for melanoma
Here is a brief review as well as reports from a study where T-VEC was combined with pembro, another with T-VEC and ipi, ipi given with IL2, as well as a report from the CALM study [don't you love their names????!!!] in which the coxsackievirus (CAVATAK) was administered singly:  From ASCO 2015: intralesional therapy for melanoma
Here's specifics on T-VEC:   Good News - local and systemic response to T-VEC
Here's the low-down on PV-10:  ASCO 2014: Rose Bengal (PV-10) with additional links
T-VEC combined with ipi: Pick your poison: Weber and Agarwala
     "When ipi is combined with T-VEC (an intralesional therapy) you get a better response rate...about 55% combined complete and partial responses....than with either drug alone." truth....I am putting this together for my dear friend, I am going to focus on an option he is looking at....CAVATAK with ipi.

Here is info from the CAVATAK only, CALM trial:

 Final data from CALM: A phase II study of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma.  ASCO - J Clin Oncol 33, 2015.  Andtbacka, Curti, Kaufman, Daniels, et al.

"CVA21 is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21.  Intratumal injection initiates preferential tumor cell infection, cell lysis [death] and enhancement of a systemic anti-tumor immune response.  The CALM study looked at 57 patients with treated or untreated, unresectable Stage IIIC-IV melanoma.  Patients were given injections on study days 1, 3, 5, 8, and 22, then every 3 weeks for a further 6 injections.  Patients showing immune-related progression-free survival or better at 6 months were eligible for 9 additional injections.  RESULTS:  21 of 57 (38%) patients displayed progression free survival at 6 months with median PFS of 4.2 months.  Overall response rate was 28% (16 of 57) with a more than 6 month durable response rate of 19% (11 of 57).  Median time to response was 2.8 months, 1 year survival rate was 75% (43 of 57 patients).  At more than 16 months, median duration of response in responders and median overall survival for all patients was not yet reached.  Most common side effects = Grade 1 fatigue, chills, local injection site reaction, and fever.  No grade 3 or 4 reactions.  Further studies with CVA21 in combination with other immunotherapies are in process."

And this link/synopsis of Weber's "What's new in 2016" talk...discusses what's coming and recent in melanoma care as well as CALM results:  Immunology update webinar for melanoma
Within...this blurb is included:  
Intralesional Immunotherapy With Oncolytic Coxsackievirus A21 (CVA21) 
 Final response and safety data of the open-label, multicenter phaseII CALM (CAVATAK in Late-stageMelanoma) study of intratumoral CVA21 in 57 patients with unresectable stage IIIC/IV melanoma.    The study met its primary endpoint.  22 of 57 (38.6%) evaluable patients with PFS at 6 months.    Median PFS of 4.2 mos.   ORR 28.1%; median TTR 2.8 mos.  1-year survival rate 75.4%.  Median OS and median DOR not reached (16.5 mos follow-up).  Most common AEs were grade 1 fatigue, chills, fever, and injection site reactions; no grade 3/4 AEs observed.  Looks like another promising intralesional therapy.  Will soon have phase 3 study.

A link to one other report:   Viralytics reports positive final results from cavatak phase 2 melanoma trial

Here is a link to:  Intratumoral CAVATAK and ipi trial
Apparently folks will get ipi at 3mg/kg 4 times.  You have to have an injectable tumor (per their criteria) and CAVATAK will be injected 4 specific times and then every three weeks for up to one year.  The study is a Phase 1 trial, sponsored by Viralytics and was started in late 2014. You can't have taken ipi for metastatic melanoma, but you can have taken it as an adjuvant as long as you did not experience a grade 3 toxicity.  Trial is recruiting in California, Oregon and Illinois.

CAVATAK is also being studied in bladder cancer and non-small-cell lung cancer.  There is also a study combining CAVATAK with pembro for melanoma.  Here's the link:  Intratumoral cavatak and pembro trial  Here folks will get CAVATAK injections at specific times up to 19 total injections into "at least one cutaneous, subcutaneous tumor or palpable lymph node amenable to intratumoral injection" and pembro infusions every 3 weeks up to 2 years. Exclusions include:  no corticosteriods, ocular or mucosal melanoma.  No prior anti-PD1 or PDL1.  Also sponsored by Viralytics, recruiting in New Jersey.

Guess that's about all I got.  I have always been a fan of intralesional therapy...telling B that if I ever recur...and have to have some sort of surgery...I was going to beg to have Rose Bengal and lord knows what else...just splashed around in there before they sew me up.  Those who know B can imagine the big blue eye roll that comment gets me....but there you go!!!  Love you, Josh!  - c

1 comment:

  1. Celeste...thank you from the bottom of my heart. You're truly a blessing to all of us especially me!! Love you!!!