2022 ASCO GI | DESTINY-CRC01 study: DS-8201 is expected to treat HER2-positive metastatic colorectal cancer

The 2022 American Society of Clinical Oncology Symposium on Gastrointestinal Oncology (ASCO-GI) will be held from January 20 to 22 local time
.

DESTINY-CRC01, a phase II, multicenter, open-label study in patients with HER2-positive metastatic colorectal cancer, reported good efficacy and safety of the antibody-conjugated drug Trastuzumab deruxtecan (T-DXd; DS-8201) Controllable, the following is the research details
.

Background Trastuzumab deruxtecan (T-DXd; DS-8201) is an anti-HER2 antibody-drug conjugate (ADC)
.

T-DXd consists of a humanized anti-HER2 antibody, an enzymatically cleaved peptide linker and a topoisomerase I inhibitor
.

DESTINY-CRC01 (DS8201-A-J203; NCT03384940) is a phase II, open-label, multicenter study
.

Preliminary analysis of T-DXd in patients with HER2-positive mCRC showed some antitumor activity and manageable safety (median follow-up [FU] of cohort A, 27.
1 weeks; Siena S, ASCO 2020)
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Updated long-term efficacy and safety data will be reported at this ASCO GI meeting
.

Methods Inclusion criteria were HER2-positive, RAS wild-type mCRC patients who had progressed after ≥2 cycles of prior regimens
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6.
4 mg/kg T-DXd was administered every 3 weeks (Q3W) in 3 cohorts (A: HER2 IHC3+ or IHC2+/ISH+; B: IHC2+/ISH; C: IHC1+)
.

The primary study endpoint was objective response rate (ORR) confirmed by independent central review in cohort
A.

Secondary endpoints were disease control rate (DCR; CR+PR+SD), duration of response (DOR), progression-free survival (PFS), and overall survival (OS)
.

Results As of December 28, 2020, 86 patients (A: n=53; B: n=15; C: n=18) received T-DXd treatment
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The median age was 58.
5 years (27-79 years), 53.
5% were male, and 90.
7% had left-sided colon or rectal cancer
.

The median number of previous lines of therapy for metastatic disease was 4 (2-11)
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All patients were treated with irinotecan, and 30.
2% of patients in cohort A had received prior anti-HER2 therapy
.

The median treatment duration for all patients was 3.
0 months (95% CI, 2.
1-4.
1; Cohort A, 5.
1 months [95% CI, 3.
9-7.
6])
.

In Cohort A (median FU, 62.
4 weeks), ORR was 45.
3% (24/53 patients; 95% CI, 31.
6-59.
6) and DCR was 83.
0% (44/53 patients; 95% CI, 70.
2- 91.
9), median DOR was 7.
0 months (95% CI, 5.
8-9.
5), median PFS was 6.
9 months (95% CI, 4.
1-8.
7), PFS events occurred in 37 cases (69.
8%), median OS At 15.
5 months (95% CI, 8.
8-20.
8), OS events occurred in 36 patients (67.
9%)
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These results are consistent with the preliminary analysis
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The ORR was 43.
8% (7/53 patients; 95% CI, 19.
8-70.
1) in patients with prior anti-HER2 therapy and 57.
5% (23/53 patients; 95% CI, 40.
9-73.
0) in IHC3+ patients, IHC2+/ISH+ patients were 7.
7% (1/53 patients; 95% CI, 0.
2-36.
0)
.

In Cohorts B and C, median PFS was 2.
1 months (95% CI, 1.
4-4.
1) and 1.
4 months (95% CI, 1.
3-2.
1); median OS was 7.
3 months (95% CI, 1.
3-2.
1), respectively 3.
0-NE) and 7.
7 months (95% CI, 2.
2-13.
9)
.

Grade ≥3 treatment-related adverse reactions (TEAEs) occurred in 65.
1% of patients (56/86)
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The most common TEAEs were blood disorders and gastrointestinal disorders
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Thirteen patients (15.
1%) discontinued treatment due to TEAEs
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Eight patients (9.
3%) had interstitial lung disease (ILD) adjudicated by an independent committee to be related to T-DXd treatment (4 grade 2; 1 grade 3; 3 grade 5)
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Conclusions In patients with HER2-positive mCRC, 6.
4 mg/kg Q3WT-DXd treatment showed certain antitumor activity and long-term treatment durability
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The safety profile is consistent with previous findings; ILD remains an important identified risk requiring rigorous monitoring and necessary intervention
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These results support continued exploration of the efficacy of T-DXd in this patient population
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Reference: Rapid Abstract Session and Poster Session 119.
Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01).