While at the ASCO meeting I viewed a large number of posters and listened to sessions reporting on the results of new immunotherapy treatments. Here are four in the initial stages of testing that caught my eye.
Poster
Board: #95 First in human phase I/II
dose escalation study of IMAB027 in
patients with recurrent advanced ovarian
cancer (OVAR): Preliminary data of
phase
I part.
Ugur
Sahin, MD
This study was done in a group of women (median age 64 years) that
had been highly pretreated, meaning they had multiple ( 4 +) prior treatments
for their disease. This Phase I/II study ( safety and dosage levels) used IMAB027
is the first-in-class monoclonal antibody (mAB) directed against claudin 6
(CLDN6), a cancer stem cell marker. Claudin-6 is expressed in 55% of ovarian cancers.
The 12 women in the study were all claudin 6+.
There were some adverse events recorded but the majority were grade 1-2 (the
lower the grade the less severe the adverse effect). The first signs of
clinical activity were observed.
“Conclusions: This
is the first clinical study to show effects of a therapy targeting CLDN6. Based
on these preliminary Phase I data, IMAB027 may present a safe and well
tolerated treatment option for women with recurrent, advanced OC. This warrants
further clinical evaluation of IMAB027”
Poster
Board: #116 Phase
1 study of IMGN853, a folate receptor
alpha (FRα )targeting antibody drug conjugate (ADC)
in patients (Pts) with epithelial ovarian cancer
(EOC)
and other FRα positive solid
tumors
Hossein
Borghaei, DO, MS
This Phase 1 trial included 23 women
with platinum resistant epithelial ovarian cancer , 11 women with endometrial cancer
as well as 1 cervical, 4 non-small cell lung cancer and 5 renal cancer
patients. The study was done to determine safety, pharmacokinetics (PK – how
the drug moves through the body), tolerated dose, and evidence of activity of
IMGN853 in ovarian cancer or other FRa-positive solid tumors.
“IMGN853
(mirvetuximab soravtansine) is a folate receptor α-targeting anti-body drug
conjugate (ADC ) comprising a FRα-binding antibody and potent maytansinoid,
DM4.”
In other words, IMGN853 binds to Folate Receptor α on cancer cells and is internalized; the DM4 ( a
tubulin-acting agent) is released through the degradation of the antibody and
it disrupts cell division and causes cell death. Two different schedules were
used (A) once every 3 weeks and (B) Days 1, 8, and 15, every 4
weeks. The adverse effects were mostly grade 1 or 2. Initial results show partial and complete
clinical response as well as CA-125
response. In A schedule, 11 of 44 patients showed complete response(CB), 4/44
showed partial response(PR) and 5 showed
stable disease (SD) . Using schedule B,
5/15 showed CR, 1 PR, 4 SD.
"Conclusion:
With both schedules,IMGN853 demonstrates encouraging clinical activity in
heavily pretreated patients during dose escalation with a manageable AE
profile. A RP2D has been identified for schedule A, while schedule B continues
dose finding."
The following results were presented in a
session called
Intersection of Mutanome and the Immunome on Monday afternoon.
Avelumab
(MSB0010718C), an antiPDL1 antibody, in
patients with previously treated, recurrent
or refractory ovarian cancer: A phase
Ib, open-label expansion trial.
Mary
L. Disis
 |
| Slide on Avelumab from Dr Disis' presention |
Avelumab (MSB0010718C) is a human anti-PD-L1 IgG1
antibody. PD-1 is a programmed death -1
receptor and PD-L1 is it’s ligand ( protein) are targets that can help to
reactivate a person’s immune system.
The patients enrolled in this Phase 1b
study were not chosen based on PDL-1 expression. All patients had recurrent
ovarian cancer and had multiple prior treatments. 52% of the patients reported
adverse effects mostly fatigue, nausea, chills and diarrhea . Of the 23
patients currently enrolled and followed for 2-8 months, 4 patients showed best overall response, 11
had stable disease and 4 had a shrinkage of their tumor of >30%. During the
presentation it was reported that patients who had smaller tumor burdens had a
better response.
"Conclusions: These data represent the largest
reported dataset of patients with recurrent ovarian cancer treated with
anti-PD-L1 therapy. Avelumab demonstrated an acceptable safety profile and is
clinically active in this heavily pretreated ovarian cancer pt population."
Antitumor
activity and safety of pembrolizumab in
patients (pts) with PD-L1 positive
advanced ovarian cancer: Interim results
from a phase Ib study
Andrea
Varga, MD
 |
| Slide from Dr Varga's presentation |
This was the second of two presentations on anti-PDL-1
immunotherapy treatments that I heard. Pembrolizumab is a monoclonal antibody
against PD-1 and blocks the interaction of PD-L1 and PD-L2 . It also removes
any blockage by the cancer cells of the body’s T-cells. T-cells are part of
your body’s immune response to cancer. This study unlike the previous study
with Avelumab was with women who were determined to be PD-l+. They received
10mg/kg of Pembrolizumab every two weeks. Twenty-six patients (median age 56)
were enrolled. Over 80% had prior
treatments. There were no grade 4 or 5 adverse effects. Reported effects
include fatigue, anemia and loss of
appetite. One patient had complete response, 2 had partial response and 6 had
stable disease. 23% of the patients had experienced a decrease in their
targeted lesions.
"Conclusions: PD-1 blockade with pembrolizumab is
well tolerated and has antitumor activity in pts with advanced ovarian cancer.
This preliminary signal for clinical efficacy will be further investigated."
Note:To learn more about pembrolizumab ( Keytruda) , which is approved
for melanoma visit https://www.keytruda.com/melanoma/how-keytruda-works/index.xhtml
These handful of studies are just the tip of the iceburg when it
comes to targeted immunotherapy treatments for gynecologic cancers. I look
forward to hearing the results of future Phase II and III studies.
In the next post I will write about the session I heard on Managing
Ovarian Cancer in the Older Patient.
Dee
Every Day is a Blessing!
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