Clinical
activity and safety of pegylated human IL-10 (AM0010) in combination with
anti-PD1. ASCO 2016. #
3018. J Clin Oncol 34, 2016. Naing, Papadopoulos, Infante, et al.
Background: IL-10 has anti-inflammatory
properties but stimulates the cytotoxicity and proliferation of CD8 T cells.
The observation that T cell receptor mediated activation induces the expression
of IL-10 receptors and PD1 on CD8 T cells, provides the mechanistic rationale
for combining AM0010 and anti-PD1 in the clinic. Tolerability and anti-tumor
activity of AM0010 alone was established in the ongoing phase 1 study.
Objective responses were observed in pts with uveal melanoma, cutaneous T cell
lymphoma and in 4 of 15 pts with RCC. Methods: Pts with advanced
melanoma, RCC or NSCLC were treated with AM0010 (daily SC) and Pembrolizumab
(q3wk IV). Tumor responses were monitored following irRC. Immune responses were
measured by analysis of serum cytokines, activation of blood derived T cells,
peripheral T cell clonality and immunohistochemistry of tumor infiltrating CD8
T cells. Results: In 19 pts, AM0010 10 mg/kg (n=13) or 20 mg/kg (n=6) in
combination with anti-PD1 (2mg/kg) was well tolerated (observation period 10-15
months). All TrAEs were transient and DLTs or TrAEs leading to study
discontinuation were not observed. There was no colitis, pneumonitis, or
endocrine disruptions. G3/4 TrAEs were observed in 7 of 19 pts and included
pruritus (1), anemia (3), thrombocytopenia (3) and malaise (1). Objective
responses (PR/CR) were observed in 4 of 8 RCC pts, 2 of 5 NSCLC pts and 2 of 6
melanoma pts. 2 additional melanoma pts had tumor increase followed by decrease
(pseudoprogression). AM0010 / anti-PD1 increased Th1 cytokines (IL-18, IFNg,
IL-7) and the number and proliferation of PD1+ activated CD8 T cells while
decreasing the proliferation of FoxP3+ Tregs and TGFb in the blood. AM0010 /
anti-PD1 induced de-novo oligoclonal expansion of T cell clones in the blood
without affecting total lymphocyte counts. AM0010 / anti-PD1 increased the
number of tumor infiltrating Granzyme+ PD1+ CD8+ T cells in tumor biopsies of
treated patients. Conclusions: AM0010 in combination with anti-PD1 is
well-tolerated. The clinical activity and the observed CD8 T cell activation
encourages the continued exploration of AM0010 in combination with anti-PD1.
Clinical trial information: NCT02009449
Best Response
|
SD
|
PR
|
CR
|
CBR
(SD, PR, CR: > 24 weeks) |
RCC
(n=8)
|
4
|
3
|
1
|
5
|
NSCLC
(n=5)
|
3
|
2
|
-
|
4
|
Melanoma
(n=6)
|
2
|
2
|
-
|
2
(NR)
|
Thanks Celeste I am looking for news from ASCO on any new treatment options for 3B. I go for my scans on June 15 and will meet with the oncologist. It is looking like ipi. Oh well better than nothing..
ReplyDeleteDid you see this post?
ReplyDeletehttp://chaoticallypreciselifeloveandmelanoma.blogspot.com/2016/06/asco-2016-two-adjuvant-studies-for.html
Looks like these studies are still enroĺling....if you are interested.
That is exactly what I want but I am 3b.
ReplyDeleteThanks again for your help...Your blog and posts are so helpful. I am very grateful.
"Stages IIIA(N2), IIIB, IIIC and IV (M1a, b and c) are eligible..." from the first study listed!!!!!
ReplyDelete