[Slide 1]
NRG
Study Design
ONCOLOGY
Marring Annual Improving Check
FFX/Bevacizumab
FFX/bevacizumab
dMMR/MSI-H mCRC without prior systemic
R
+
treatment for metastatic disease*
Atezolizumab+
Randomization 1:1:1 (then 1:1)
Stratified according to:
Atezolizumab*
BRAF mutation (V600E; non-V600E, WT, or Unknown)
Metastatic disease: (liver-only; extra-hepatic)
Prior adjuvant therapy for CRC
* One cycle of FOLFOX or CAPOX with or without
bev (or biosimilar) allowed prior to enrollment
t FFX/bev/atezo: oxaliplatin 85 mg/m2 IV +
leucovorin 400 mg/m2 IV + bevacizumab 5
mg/kg IV+ 5-FU 400 mg/m2 IV bolus on Day 1
followed by 5-FU 2400 mg/m2 IV over 46 hours
plus atezo (840mg IV q2wks)
# Atezo monotherapy: 840mg IV q2wks
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali wakehealth edu for permission to reprint and/or distribute.
---
[Slide 2]
NRG
Progression-free Survival
ONCOLOGY
belowing Frown -
1.0
HR 0.439; 95% CI 0.23-0.84; P =0.0103
0.8
Median PFS (months)
0.6
Survival Probability
24.5 (95% CI, 10.1-not estimable)
0.4
5.3 (95% CI, 2.2-18.2)
0.2
0.0
Atezo
40
12
9
6
5
5
1
FFX/bev/atezo
38
24
17
13
9
6
4
0
10
20
30
40
50
60
Months
Atezo
FFX/bev/atezo
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali wakehealth. edu for permission to reprint and/or distribute.
---
[Slide 3]
NRG
Additional Efficacy Outcomes
ONCOLOGY
Branch Improving -
Efficacy Outcome
FFX/bev/atezo
Atezo
Progression-free Survival
12 months
66.7%
35.1%
24 months
53.7%
31.6%
Overall Response Rate
86.1%
46%
Response Status
CR
36.1%
18.9%
PR
50%
27%
SD
11.1%
21.6%
PD
2.8%
32.4%
Disease Control Rate
12 months
64.7%
32.4%
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali wakehealth edu for permission to reprint and/or distribute.
---
[Slide 4]
NRG
Conclusions
ONCOLOGY
Advancing importing -
The combination of FFX/bev/atezo demonstrated a statistically significant
improvement in PFS compared to atezo monotherapy in the first-line
setting for dMMR/MSI-H mCRC
HR 0.439; 95% CI 0.23-0.84, P=0.0103
FFX/bev/atezo resulted in improved complete responses and reduced
progressive disease compared to atezo monotherapy
Complete response: 36.1% vs 18.9%
Progressive disease: 2.8% vs 32.4%
Higher rates of G3-4 diarrhea, neutropenia, hypertension, and infection
observed in the FFX/bev/atezo arm
Future efforts are needed to characterize the subsets of dMMR/MSI-H CRC
that require intensification of therapy beyond single-agent PD-1/PD-L1
therapy.
Ongoing correlative analyses will hopefully provide deeper mechanistic
interpretation of the differential outcomes across treatment arms.
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali wakehealth edu for permission to reprint and/or distribute.
[Slide 1]
NRG
Study Design
ONCOLOGY
Advancing Research Improving Lines*
FFX/bevacizumab
dMMR/MSI-H mCRC without prior systemic
R
+
treatment for metastatic disease*
Atezolizumab+
Randomization 1:1:1 (then 1:1)
Stratified according to:
Atezolizumab
BRAF mutation (V600E; non-V600E, WT, or Unknown)
Metastatic disease: (liver-only; extra-hepatic)
Prior adjuvant therapy for CRC
* One cycle of FOLFOX or CAPOX with or without
bev (or biosimilar) allowed prior to enrollment
Due to KEYNOTE 177 results, COMMIT's FFX/bev arm was closed (trial
t FFX/bev/atezo: oxaliplatin 85 mg/m2 IV +
amended 6/4/20), leaving two arms:
leucovorin 400 mg/m2 IV + bevacizumab 5
mg/kg IV+ 5-FU 400 mg/m2 IV bolus on Day 1
FFX/bev/atezo
followed by 5-FU 2400 mg/m2 IV over 46 hours
Atezo monotherapy
plus atezo (840mg IV q2wks)
# Atezo monotherapy: 840mg IV q2wks
The study was also modified to enroll 120 total patients.
80% power to detect a hazard ratio of 0.6 for PFS, one-sided
alpha=0.025.
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali wakehealth. for permission to reprint and/or distribute.
---
[Slide 2]
NRG
Progression-free Survival
ONCOLOGY
Advancing Research Improving Lines"
1.0
HR 0.439; 95% CI 0.23-0.84; P =0.0103
0.8
Median PFS (months)
0.6
Survival Probability
24.5 (95% CI, 10.1-not estimable)
0.4
5.3 (95% CI, 2.2-18.2)
0.2
0.0
Atezo
40
12
9
6
5
5
1
FFX/bev/atezo
38
24
17
13
9
6
4
0
10
20
30
40
50
60
Months
Atezo
FFX/bev/atezo
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali@wakehealth.edu for permission to reprint and/or distribute.
---
[Slide 3]
NRG
Overall Survival
ONCOLOGY
Advancing Research. Improving Lives
1.0
There was no difference
0.8
in os between the arms:
HR of 1.04
0.6
(95% CI, 0.47-2.28, P
Survival Probability
= 0.90)
0.4
24-month OS:
0.2
FFX/bev/atezo: 67%
Atezo: 67%
0.0
Atezo
41
29
22
18
14
11
5
FFX/bev/atezo
41
30
24
20
14
11
8
0
10
20
30
40
50
60
Months
Atezo
FFX/bev/atezo
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali@wakehealth.edu for permission to reprint and/or distribute.
---
[Slide 4]
NRG
Conclusions
ONCOLOGY
Advancing Research Improving Lives
The combination of FFX/bev/atezo demonstrated a statistically significant
improvement in PFS compared to atezo monotherapy in the first-line
setting for dMMR/MSI-H mCRC
HR 0.439; 95% CI 0.23-0.84, P=0.0103
FFX/bev/atezo resulted in improved complete responses and reduced
progressive disease compared to atezo monotherapy
Complete response: 36.1% vs 18.9%
Progressive disease: 2.8% vs 32.4%
Higher rates of G3-4 diarrhea, neutropenia, hypertension, and infection
observed in the FFX/bev/atezo arm
Future efforts are needed to characterize the subsets of dMMR/MSI-H CRC
that require intensification of therapy beyond single-agent PD-1/PD-L1
therapy.
Ongoing correlative analyses will hopefully provide deeper mechanistic
interpretation of the differential outcomes across treatment arms.
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali@wakehealth. edu for permission to reprint and/or distribute.
[Slide 1]
NRG
Study Design
ONCOLOGY
discussing Previde dispensing -
FFX/bevacizumab
dMMR/MSI-H mCRC without prior systemic
R
+
treatment for metastatic disease*
Atezolizumab+
Randomization 1:1:1 (then 1:1)
Stratified according to:
Atezolizumab
BRAFmutation (V600E; non-V600E, WT, or Unknown)
Metastatic disease: (liver-only; extra-hepatic)
Prior adjuvant therapy for CRC
*
One cycle of FOLFOX or CAPOX with or without
bev (or biosimilar) allowed prior to enrollment
Due to KEYNOTE 177 results, COMMIT's FFX/bev arm was closed (trial
t
FFX/bev/atezo: oxaliplatin 85 mg/m2 IV +
amended 6/4/20), leaving two arms:
leucovorin 400 mg/m2 IV + bevacizumab 5
mg/kg IV+ 5-FU 400 mg/m2 IV bolus on Day 1
FFX/bev/atezo
followed by 5-FU 2400 mg/m2 IV over 46 hours
Atezo monotherapy
plus atezo (840mg IV q2wks)
$ Atezo monotherapy: 840mg IV q2wks
The study was also modified to enroll 120 total patients.
80% power to detect a hazard ratio of 0.6 for PFS, one-sided
alpha=0.025.
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at croshali@ wakehealth edu for permission to reprint and/or distribute.
ASCO Gastrointestinal
Cancers Symposium
---
[Slide 2]
NRG
Study Suspension/Pre-planned Interim Analysis
ONCOLOGY
Advancing Board beforeing -
Accrual suspended March 31, 2025, because of the results from the
Checkmate 8HW trial.
A pre-planned interim analysis occurred near the same time.
A total of 102 patients enrolled from 11/2017 to 3/2025.
FFX/bev: n=20
FFX/bev/atezo: n=41
}
Statistical Analytic Population
Atezo: n=41
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at trochalie wakehealth edu for permission to reprint and/or distribute.
ASCO Gastrointestinal
Cancers Symposium
---
[Slide 3]
NRG
Progression-free Survival
ONCOLOGY
Advancing Road before -
1.0
HR 0.439; 95% CI 0.23-0.84; P =0.0103
0.8
Median PFS (months)
0.6
Survival Probability
24.5 (95% CI, 10.1-not estimable)
0.4
5.3 (95% CI, 2.2-18.2)
0.2
0.0
Atezo
40
12
9
6
5
5
1
FFX/bev/atezo
38
24
17
13
9
6
4
0
10
20
30
40
50
60
Months
Atezo
FFX/bev/atezo
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation IS the intellectual property of the author. Contact Dr. Rocha Lima at crothali@wakehealth edu for permission to reprint and/or distribute.
ASCO G
---
[Slide 4]
NRG
Conclusions
ONCOLOGY
howing bounk -
The combination of FFX/bev/atezo demonstrated a statistically significant
improvement in PFS compared to atezo monotherapy in the first-line
setting for dMMR/MSI-H mCRC
HR 0.439; 95% CI 0.23-0.84, P=0.0103
FFX/bev/atezo resulted in improved complete responses and reduced
progressive disease compared to atezo monotherapy
Complete response: 36.1% vs 18.9%
Progressive disease: 2.8% vs 32.4%
Higher rates of G3-4 diarrhea, neutropenia, hypertension, and infection
observed in the FFX/bev/atezo arm
Future efforts are needed to characterize the subsets of dMMR/MSI-H CRC
that require intensification of therapy beyond single-agent PD-1/PD-L1
therapy.
Ongoing correlative analyses will hopefully provide deeper mechanistic
interpretation of the differential outcomes across treatment arms.
ASCO Gastrointestinal
Jan 8-10, 2026
Cancers Symposium
This presentation is the intellectual property of the author. Contact Dr. Rocha Lima at crochali wakehealth edu for permission to reprint and/or distribute.
ASCO Gastrointe
Cancers Symposi
COMMIT (NRG-GI004/SWOG-S1610) is a Phase III, randomized, multicenter trial evaluating whether adding standard chemotherapy (mFOLFOX6) and anti-VEGF therapy (bevacizumab) to immunotherapy (atezolizumab) can improve outcomes compared with immunotherapy alone in the first-line treatment of dMMR/MSI-H metastatic colorectal cancer. Presented at ASCO GI 2026, the trial demonstrated a significant PFS benefit for the triplet combination, addressing the ~40% primary resistance rate seen with immune checkpoint inhibitor monotherapy in KEYNOTE-177.
Phase III, randomized, multicenter trial (NCT02997228). Originally three arms: atezolizumab monotherapy, atezolizumab + mFOLFOX6 + bevacizumab, and mFOLFOX6 + bevacizumab alone. The chemo-only arm was discontinued in June 2020 after KEYNOTE-177 established ICI as standard of care. Final analysis compared 102 patients randomized between the two atezolizumab-containing arms. Atezolizumab 840 mg IV every 2 weeks; mFOLFOX6 standard dosing; bevacizumab 5 mg/kg.
Population
Previously untreated patients with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer. No prior systemic therapy for metastatic disease.
Interventions
Atezolizumab 840 mg IV every 2 weeks (monotherapy arm) versus atezolizumab 840 mg IV every 2 weeks plus mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) plus bevacizumab 5 mg/kg (triplet arm).
Primary Endpoints
Primary endpoint: PFS comparing atezolizumab monotherapy vs. the triplet combination. The study was designed with 80% power to detect HR 0.6, with preplanned interim analysis. The DSMC recommended closing the study early after the primary endpoint was met at interim analysis.
Progression-Free Survival (PFS)
The triplet combination of atezolizumab + mFOLFOX6 + bevacizumab significantly improved PFS versus atezolizumab monotherapy. PFS HR was 0.439 (95% CI: 0.23-0.84; p=0.0103), representing a 56% reduction in the risk of disease progression or death. Median PFS: 24.5 months (95% CI: 10.1-NE) vs. 5.3 months for monotherapy (alternative reporting: 30.0 months vs. 4.3 months). 12-month PFS rate: 66.7% vs. 35.1%. 24-month PFS rate: 53.7% vs. 31.6%. The triplet achieved ORR of 80.6-86.1% vs. 46%, with CR rate 36.1% vs. 18.9%. Critically, primary progressive disease was only 2.8% in the combination arm vs. 32.4% with monotherapy.
At the interim analysis (median follow-up 3.5 years), no significant difference in OS was observed between the two arms (HR 1.04; 95% CI: 0.47-2.28; p=0.90). Longer-term follow-up for OS is ongoing.
The triplet combination was associated with significantly higher toxicity. Any-grade AEs: 92.7% (combination) vs. 80.5% (monotherapy). Grade 3-4 AEs: 73.2% vs. 41.5%. Key Grade 3-4 AEs in the combination arm: neutropenia (26.8% vs. 0%), infection (26.8% vs. 12.2%), hypertension (19.5% vs. 2.4%), diarrhea (12.2% vs. 0%). Five grade 5 AEs were recorded: 4 in the combination arm (1 disease progression, 2 sudden deaths, 1 hepatic hemorrhage post-resection) and 1 in the monotherapy arm (disease progression).
Higher toxicity with triplet — G3/4 AEs 73% vs. 42%
COMMIT addresses a critical clinical problem: ~40% of dMMR/MSI-H mCRC patients experience primary resistance to ICI monotherapy. The triplet combination virtually eliminated early progression (2.8% vs. 32.4%) and dramatically improved response rates and PFS. However, this came at the cost of significantly higher toxicity with no OS benefit at interim analysis. The key clinical debate centers on patient selection: the triplet may be most beneficial for patients with bulky, aggressive, or visceral-crisis disease where early control is critical, while ICI monotherapy may remain preferred for patients who can tolerate the risk of slower initial response. Biomarker identification for primary resistance to ICI remains an urgent unmet need.
