ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been granted two additional Breakthrough Therapy Designations (BTDs) in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, and for the treatment of patients with HER2 positive (IHC 3+) metastatic colorectal cancer who have received two or more prior regimens.

...ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.

...Number of Participants With Best Objective Response Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer`Objective response rate (defined as CR+PR) was reported based on independent central review. ...

Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively….These promising results support the investigation of T-DXd in earlier lines of therapy and the continued exploration of T-DXd in patients with HER2-positive mCRC.

Confirmed ORR was 43.8% (7/53 pts; 95% CI, 19.8-70.1) for pts with prior anti-HER2 therapy, 57.5% (23/53 pts; 95% CI, 40.9-73.0) for pts with IHC3+ status, and 7.7% (1/53 pts; 95% CI, 0.2-36.0) for pts with IHC2+/ISH+ status. In cohorts B and C, mPFS was 2.1 mo (95% CI, 1.4-4.1) and 1.4 mo (95% CI, 1.3-2.1); mOS was 7.3 mo (95% CI, 3.0-NE) and 7.7 mo (95% CI, 2.2-13.9), respectively....T-DXd at 6.4 mg/kg Q3W showed promising activity and durability with longer-term FU in pts with HER2-expressing mCRC.

Pts with centrally confirmed HER2-expressing, RAS wildtype mCRC that progressed after ≥2 prior regimens received 6.4 mg/kg of T-DXd...In cohort A, higher clinical response to T-DXd was observed with higher tumor or plasma HER2 expression...

Pts had centrally confirmed HER2-expressing, RAS wild-type mCRC that progressed after ≥2 prior regimens…In cohort A (median FU, 62.4 weeks), confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6-59.6), DCR was 83.0% (44/53 pts; 95% CI, 70.2-91.9), mDOR was 7.0 mo (95% CI, 5.8-9.5), mPFS was 6.9 mo....T-DXd at 6.4 mg/kg Q3W showed promising activity and durability with longer-term FU in this pt population...These results support continued exploration of T-DXd in pts with HER2-overexpressing mCRC.

Pts with centrally confirmed HER2-expressing, RAS–wild type mCRC that progressed on ≥ 2 prior regimens received T-DXd 6.4 mg/kg every 3 weeks (q3w) in 3 cohorts (A: HER2 IHC 3+ or IHC 2+/ISH+; B: IHC 2+/ISH−; C: IHC 1+)...The confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6%-59.6%) in cohort A, including 1 CR and 23 PRs; median DOR was not reached (95% CI, 4.2 mo-NE). The ORR in pts with prior anti-HER2 treatment was 43.8% (7/16 pts; 95% CI, 19.8%-70.1%). The DCR was 83.0% (44/53 pts; 95% CI, 70.2%-91.9%); median PFS was 6.9 mo (95% CI, 4.1 mo-NE); median OS was not reached. No responses were observed in cohorts B or C.

In the HER2-expressing or HER2-mutant colorectal cancer subgroup, 5.0% (1/20) of patients had a confirmed objective response. A total of 85.0% of patients with colorectal cancer (17/20) had a PFS event, and the median PFS was 4.0 (95% CI, 2.7–5.6) months (Fig. 2). Among 9 patients with HER2 IHC 3+ colorectal cancer, the confirmed ORR was 11.1% (1/9) and the confirmed DCR was 100% (9/9).

As of Apr 18, 2018, 19 HER2-expressing CRC sbj received ≥1 dose of DS-8201a... Nine of 15 (60.0%) sbj with ≥1 post baseline scan experienced tumor shrinkage….DS-8201a demonstrated antitumor activity with manageable safety profile in heavily pretreated subjects with HER2-expressing CRC...