On November 14, 2022 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) ("Infinity" or the "Company"), a clinical-stage biotechnology company developing eganelisib, a first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported an update from its MARIO-3 study of eganelisib in combination with atezolizumab and nab-paclitaxel in front-line metastatic triple negative breast cancer (TNBC) patients (Press release, Infinity Pharmaceuticals, NOV 14, 2022, View Source [SID1234623995]).
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"Given our goal of improving long-term patient outcomes, we are particularly pleased to see that the addition of eganelisib to standard of care therapy showed benefit in the one-year progression free survival rate in MARIO-3 regardless of PD-L1 status," said Robert Ilaria, Jr., MD, Chief Medical Officer of Infinity. "These data reinforce the positive two-year landmark overall survival data from MARIO-275 in 2L urothelial cancer, also regardless of PD-L1 status, and the encouraging PFS observed in checkpoint inhibitor refractory squamous cell cancer of the head and neck in our MARIO-1 study, which all support the potential of eganelisib to improve long term outcomes for patients."
MARIO-3 mTNBC Updated Data:
62 patients were enrolled and evaluable for safety, and 57 patients were evaluable for efficacy, with a median duration of follow-up of 10.0 (8.1,14.2) months. Of the 57 evaluable patients:
35 patients (61.4%) had PD-L1(-) tumors
18 patients (31.6%) had PD-L1(+) tumors
4 patients (7.0%) had tumors of undetermined PD-L1 status
With an additional year of data maturity since the San Antonio Breast Cancer Symposium 2021, there is now encouraging evidence of a long-term patient progression-free survival (PFS) benefit with improved one-year PFS rates in MARIO-3, including in patients with both PD-L1(+) and PD-L1(-) tumors, compared to the benchmark IMpassion130 study.
ITT
PD-L1 (+)
PD-L1 (-)
MARIO-3
n=57^
IMpassion130
n=451^^
MARIO-3
n=18
IMpassion130
n=185
MARIO-3
n=35
IMpassion130
n=266
One-Year PFS Rate, % (95% CI)
36.0%
(23.7, 49.3)
23.7%
(19.6, 27.9)
37.5%
(16.8, 60.9)
29.1%
(22.2, 36.1)
34.7%
(19.6, 51.6)
NR*
One-Year PFS Rate improvement compared to IMpassion130
52%
relative improvement
29%
relative improvement
NE**
[46% relative improvement compared to IMpassion130 ITT]
Median duration of follow up, months (95% CI)
10.0
(8.1, 14.2)
13.0
(NR*)
9.9
(5.5, NA)
NR*
9.3
(5.9, 14.2)
NR*
Data Snapshot: 8 October 2022
^4 patients of unknown PD-L1 status
^^ Schmid et al NEJM 2018
* NR = Not Reported
**NE = Not Evaluable
Additional data from the MARIO-3 study, by patient population and relative to IMpassion130 benchmarks:
PD-L1 (+)
PD-L1 (-)
MARIO-3
n=18
IMpassion130^
n=185
MARIO-3
n=35
IMpassion130^
n=265
CR, % (n)^^
16.7 (3)
10.3 (19)
5.7 (2)
4.9 (13)
ORR, % (n)^^
66.7 (12)
58.9 (109)
54.3 (19)
54.0 (143)
mDOR (mos) n (95% CI)^
11.7
n=12
(1.8, NA)
8.5
n=109
(7.3, 9.7)
7.4
n=19
(3.7, NA)
NR*
mDOR increase compared to IMpassion130
3.2 mos
(37.6% increase)
NE**
mPFS, mos
(95% CI)
6.4
(3.6, NA)
7.5
(6.7, 9.2)
7.3
(5.2, 13.3)
5.6
(5.5, 7.3)
Data Snapshot: 8 October 2022
^Schmid et al NEJM 2018 with PD-L1(-) data calculated based on ITT and PD-L1(+) data
^^ Includes unconfirmed and confirmed responses for MARIO-3
*NR = Not Reported
** NE = Not Evaluable
No new safety signals were observed during the extended period on treatment, and the MARIO-3 safety profile continued to be consistent with expectations for the three component drugs.
Most Common Treatment-Related TEAEs in ≥ 10% of All Treated Patients^* (n=62)
Preferred
Term/Grouped Term
Treatment
related TEAE
(All), n (%)
Treatment-related
TEAE (≥ Gr. 3),
n (%)
Fatigue
30 (48.4)
4 (6.5)
Skin AEs
29 (46.8)
7 (11.3)
Nausea
28 (45.2)
0 (0.0)
Hepatic AEs**
24 (38.7)
15 (24.2)
Diarrhea
18 (29.0)
3 (4.8)
Alopecia
16 (25.8)
0 (0.0)
Neutropenia AEs
16 (25.8)
9 (14.5)
Vomiting
13(21.0)
1 (1.6)
Pyrexia
10 (16.1)
0 (0.0)
Peripheral neuropathy
19 (30.6)
7 (11.3)
Stomatitis
9 (14.5)
0 (0.0)
Decreased appetite
8 (12.9)
0 (0.0)
Headache
8 (12.9)
0 (0.0)
Weight decreased
7 (11.3)
1 (1.6)
Dysgeusia
7 (11.3)
0 (0.0)
Constipation
7 (11.3)
0 (0.0)
Data Snapshot: 23 July 2022
Presented in descending order of All Treatment-Related TEAE
^ Treatment-related is related to any of the study drugs (eganelisib, atezolizumab, nab-paclitaxel)
* No treatment-related Grade 5 AEs
** One Grade 4 event and no event met Hy’s Law criteria
Hepatic, skin, neutropenia, and peripheral neuropathy represent grouped preferred terms.
Treatment Discontinuation:
74% of patients were able to remain on treatment with the MARIO-3 TNBC triplet regimen compared to 81% of patients with the IMpassion130 doublet.