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A multicenter, phase 2 study to evaluate safety and efficacy of panitumumab re-challenge based on circulating tumor DNA analysis in patients with RAS/BRAF V600E wild-type unresectable metastatic colorectal cancer with prior treatment history of anti-EGFR antibody (PURSUIT)

Panitumumab re-challenge strategy for liquid RAS mutation negative metastatic colorectal cancer (PURSUIT)

50

Age, years : Median (range) 68 (52-72) Gender : Male/Female 32/18 (64/36) ECOG PS : 0/1 28/22 (56/44) Location of primary lesion : Right/Left 6/44 (12/88) Primary lesion resection : Yes/No 34/16 (68/32) No. of metastatic sites : 0-1/>=2 16/34 (32/68) Metastatic site (overlapped) : Liver 37 (74),Lung 28 (56),Lymph nodes 25(50),Peritoneum 14 (28) Number of prior treatment regimens : 1/>=2 25/25 (50/50)

In this clinical study, informed consent was obtained from 51 patients, one of whom was a discontinued study participant at screening, so 50 patients were enrolled and received protocol treatment. All 50 enrolled patients were administered the study drug, but all patients discontinued administration due to exacerbation of the underlying disease before the completion of the 1-year study. The initial scheduled completion date for registration was September 2020, but as of May 2021.

The incidence of adverse events (including those for which a causal relationship could be ruled out) was 94.0% (47/50), and the incidence of adverse events (a causal relationship could not be ruled out) was 94.0% (47/50). There were no deaths due to adverse events. The incidence of serious adverse events was 16.0% (8/50), with decreased blood magnesium in 2 cases, appendicitis, acute kidney injury, enteritis, pyelonephritis, cholestatic jaundice, and hypersensitivity in 1 case each.

Primary endpoint: ORR was calculated by z-test with arc-sine transformation, with a point estimate and two-sided 90% confidence interval of 14.0% (90% CI 7.0%-23.0%), with a threshold response rate of 10% and The expected response rate of 25% was not achieved. Secondary endpoints: (1) The point estimate of PFS (95% confidence interval) was 3.6 (3.0 - 4.7) months. The point estimate (95% confidence interval) for 6-month progression-free survival was 18.0% (8.9% to 29.7%). (2) The point estimate of TTF (95% confidence interval) was 3.6 (3.0 - 4.7) months. The point estimate (95% confidence interval) of the 6-month treatment success rate was 18.0% (8.9%-29.7%). (3) The DoR point estimate (95% confidence interval) was 3.8 (3.3 - 5.4) months. The point estimate (95% confidence interval) of the 3-month response rate was 100.0% (100.0%-100.0%). (4) The point estimate of OS (95% confidence interval) was 12.0 (8.5 - 14.6) months. The point estimate (95% confidence interval) for 12-month overall survival was 48.0% (33.7% to 60.9%). (5) The DCR point estimate (95% confidence interval) was 80.0% (67.9% - 89.8%). (6) In the ORR of the subgroup analysis by the presence or absence of genetic abnormality, no difference was observed due to the presence or absence of RAS gene abnormality at any time point. In the PFS of the subgroup analysis, PFS was significantly longer in the mutation-negative group than in the positive group based on the blood RAS mutation determination result (=PC3 status) on Day 1 of the 3rd cycle after PURSUIT registration (p = 0.0116). The TTF of the subgroup analysis was significantly longer in the PC3 status RAS mutation-negative group than in the positive group (p = 0.0116). In the subgroup analysis, DoR, OS, and DCR showed no difference between the presence or absence of RAS gene abnormality at any time point.

The efficacy of panitumumab + irinotecan therapy as an anti-EGFR antibody rechallenge was insufficient for colorectal cancer patients who were determined to be negative for blood RAS mutations by ctDNA analysis. In the future, it was considered necessary to examine effect predictors to increase efficacy.

July. 31, 2023

June. 02, 2022

https://meetings.asco.org/abstracts-presentations/208519

No

-

https://jrct.niph.go.jp/latest-detail/jRCTs031190096

Ohta Takashi

KANSAI ROSAI HOSPITAL

3-1-69 Inabasou, Amagasaki-shi, Hyogo

tks.ohta@gmail.com

Ohta Takashi

KANSAI ROSAI HOSPITAL

3-1-69 Inabasou, Amagasaki-shi, Hyogo

+81-6-6416-1221

tks.ohta@gmail.com

Complete

Oct. 01, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1)Histological diagnosis of primary colorectal adenocarcinoma.
2)RAS(KRAS/NRAS)and BRAF V600E wild type analyzed by tumor tissue.
3)Intolerant or refractory to chemotherapy including a fluoropyrimidine, oxaliplatin and irinotecan.
4)Complete or partial response to previous chemotherapy including anti-EGFR antibody (cetuximab or panitumumab).
5)Documentation of progression to previous anti-EGFR antibody within 2 months after last anti-EGFR antibody administration.
6)Negative for plasma RAS mutant within 28 days before registration.
7)Time between the end of previous anti-EGFR antibody and the start of protocol treatment with panitumumab plus irinotecan >= 4 months.
8)Measurable disease according to RECIST guideline v1.1.
9)ECOG 0 or 1.
10)Age >= 20 year old.
11)Adequate major organ function assessed within 14 days before registration.
12)Life expectancy of at least 12 weeks.
13)Written informed consent obtained.

1)Severe comorbidity.
2)Underwent one of following treatments before protocol treatment;
a. Extensive surgery within 4 weeks.
b. Colostomy/ileostomy within 2 weeks.
c. Chemotherapy within 2 weeks.
d. Radiation therapy within 2 weeks.
3)CTCAE Grade >= 2 adverse events due to previous therapy, which are not recovered.
4)History of severe infusion reactions to anti-EGFR antibody.
5)Intolerant to previous irinotecan therapy.
6)Comorbidity or history of severe pulmonary disease.
7)Men/women who are unwilling to avoid pregnancy. Women who are pregnant or breastfeeding. Women with a positive pregnancy test.
8)Active HCV or HIV infection.
9)Any other patients who are regarded as inadequate for study enrollment by investigators.

Both

RAS/BRAF V600E wild-type unresectable metastatic colorectal cancer

Panitumumab 6 mg / kg and irinotecan 150 mg / m 2 are administered once every two weeks (14 days) until it meets protocol termination criteria.

Objective response rate:ORR
(Investigator's judgment based on RECIST guideline ver. 1.1)

Progression free survival:PFS
Time to treatment failure:TTF
Duration of response:DoR
Overall survival:OS
Disease control rate:DCR
Rate of adverse events
ORR, PFS, TTF, DoR, OS, DCR depending on presence or absence of each gene abnormality in ctDNA analysis at the time of discontinuation of administration before and during anti-EGFR antibody rechallenge

+81-4-7133-1111

Mar. 14, 2019

none