Table 1.
Summary of current clinical trials investigating antibody drug conjugates targeting HER2. Legend: ° Active, not recruiting; * Not yet recruiting. Abbreviations: ID, identifier; #, number; pts, patients; BC, breast cancer; mBC, metastatic breast cancer; HER2, human epidermal growth factor receptor 2; CT, chemotherapy; ET, endocrine therapy; HR, hormone receptor; TPC, treatment of physician’s choice; NSCLC, non-small cell lung cancer; mTNBC, metastatic triple negative breast cancer; eBC, early breast cancer; T-DM1, trastuzumab emtansine; PD-L1, programmed death-ligand 1. Source: ClinicalTrial.gov (accessed on 15 March 2021).
| Drug | Trial ID | Ph | # of Pts | Patient Cohort | Treatment Arms |
|---|---|---|---|---|---|
| ALT-P7 | NCT03281824 ° | I | 30 | HER2-positive mBC pretreated with trastuzumab | ALT-P7 |
| ARX788 | NCT03255070 | I | 60 | HER2-positive and HER2-low mBC; HER2-positive gastric cancer | ARX788 |
| A166 | NCT03602079 | I/II | 82 | HER2-expressing (≥1+) solid tumors (including BC) | A166 |
| BAT8001 | NCT04185649 ° | III | 410 | HER2-positive mBC pretreated with trastuzumab and a taxane | BAT8001 vs. Capecitabine + Lapatinib |
| DHES0815A (RG6148) |
NCT03451162 ° | I | 14 | HER2-positive mBC | DHES0815A |
| Disitamab Vedotin (RC-48) |
NCT04280341 * | I | 50 | Advanced HER2-positive solid tumors (including BC); standard treatment-refractory | RC-48 + JS001 (anti-PD1) |
| NCT03052634 | I/II | 111 | HER2-positive and HER2-low mBC for which no standard therapy exists | RC-48 | |
| NCT03500380 | II | 228 | HER2-positive mBC. Prior treatment with trastuzumab and taxane; up to two prior CT in advanced setting | RC-48 vs. Capecitabine + Lapatinib | |
| NCT04400695 | III | 366 | HER2-low mBC. Pretreated with one or two prior CT (anthracyclines required) and ET if HR+ | RC-48 vs. TPC | |
| FS-1502 | NCT03944499 * | I | 92 | HER2-expressing advanced solid tumors and HER2-positive mBC | FS-1502 |
| GQ1001 | NCT04450732 | I | 27 | HER2-positive advanced solid tumors (including BC) | GQ1001 |
| PF-06804103 | NCT03284723 ° | I | 148 | HER2-positive and HER-2 negative mBC | PF-06804103 +/− (Palbociclib +Letrozole) |
| Trastuzumab Deruxtecan (DS-8201a) |
NCT03523572 ° | I | 99 | HER2-positive and HER2-low mBC or urothelial cancer | T-DXd + Nivolumab |
|
NCT04556773 (DESTINY-Breast08) |
I | 185 | HER2-low mBC | T-DXd + Capecitabine T-DXd + Durvalumab and Paclitaxel T-DXd + Capivasertib T-DXd + Anastrazole T-DXd + Fulvestrant |
|
| NCT04042701 | I | 115 | HER2-positive and HER2-low mBC or HER-2-expressing/mutant NSCLC | T-DXd + Pembrolizumab | |
|
NCT04538742 (DESTINY-Breast07) |
I/II | 350 | HER2-positive mBC. At least one prior treatment line in metastatic setting required (part 1); no prior lines of therapy for advanced/mBC allowed (part 2). | T-DXd T-DXd + Durvalumab T-DXd + Pertuzumab T-DXd + Paclitaxel T-DXd + Durvalumab and paclitaxel T-DXd + Tucatinib |
|
|
NCT03742102 (BEGONIA) |
I/II | 200 | First-line treatment in mTNBC (Arm 6 HER2-low) | Durvalumab + other agents (T-DXd in Arm 6) | |
|
NCT04539938 (HER2CLIMB-04) |
II | 70 | HER2-positive mBC treated with at least two prior anti-HER2-based regimens in the metastatic setting | T-DXd + Tucatinib | |
|
NCT04752059 (TUXEDO-1) |
II | 15 | HER2-positive BC with brain metastases and prior exposure to trastuzumab and pertuzumab. | T-DXd | |
| NCT04553770 | II | 88 | HR+/HER2-low eBC candidate to neoadjuvant therapy | T-DXd +/− Anastrazole | |
|
NCT04420598 (DEBBRAH) |
II | 39 | HER2-positive or HER2-low BC with brain or leptomeningeal metastases | T-DXd | |
|
NCT04622319 (DESTINY-Breast05) |
III | 1600 | HER2-positive eBC with residual invasive disease following neoadjuvant therapy containing trastuzumab and taxane | T-DXd vs. T-DM1 | |
|
NCT04494425 (DESTINY-Breast06) |
III | 850 | HR+/HER2-low mBC. Progression on at least two previous lines of ET; no prior CT for advanced or mBC | T-DXd vs. TPC | |
|
NCT03529110 (DESTINY-Breast03) ° |
III | 500 | HER2-positive mBC previously treated with trastuzumab and a taxane | T-DXd vs. T-DM1 | |
|
NCT03734029 (DESTINY-Breast04) ° |
III | 557 | HER2-low mBC. If HR+ has progressed on ET; one to two prior CT for mBC | T-DXd vs. TPC | |
|
NCT03523585 (DESTINY-Breast02) ° |
III | 600 | HER2-positive mBC previously treated with T-DM1 | T-DXd vs. TPC | |
|
NCT04739761 * (DESTINY-Breast12) |
IV | 500 | HER2-positive mBC | T-DXd | |
| Trastuzumab Duocarmazine (SYD985) |
NCT04602117 * | I | 27 | HER2-positive and HER2-low pretreated solid tumors (only BC in expansion cohort) | SYD985 + Paclitaxel |
| NCT04235101 | I | 120 | HER2-expressing (≥1+) solid tumors (including BC) for which no standard therapy exists | SYD985 + Niraparib | |
|
NCT03262935 ° TULIP |
III | 436 | HER2-positive mBC progressed after at least two prior anti-HER2-based regimens or after T-DM1 for advanced or mBC | SYD985 vs. TPC | |
| Trastuzumab Emtansine (T-DM1) |
NCT01976169 ° | I | 28 | HER2-positive and RB-proficient mBC previously treated with anti-HER2 | T-DM1 + Palbociclib |
| NCT03032107 ° | I | 27 | HER2-positive mBC; prior treatment with trastuzumab and a taxane | T-DM1 + Pembrolizumab | |
| NCT04509596 | I | 94 | HER2-positive mBC which failed prior therapies | DZD1516 +/− Capecitabine and Trastuzumab or +/− T-DM1 | |
| NCT02236000 ° | I/II | 63 | HER2-positive mBC pretreated with trastuzumab and pertuzumab | T-DM1 + Neratinib | |
| NCT02657343 ° | I/II | 26 | HER2-positive mBC. In Cohort A: prior trastuzumab and taxane, up to four prior lines in the metastatic setting | Ribociclib + other agents (Cohort A with T-DM1) | |
| NCT03190967 | I/II | 125 | HER2-positive BC with treated brain metastases | T-DM1 +/− Metronomic Temozolomide | |
|
NCT03587740 ° (ATOP TRIAL) |
II | 82 | HER2-positive mBC in older patient (≥60 years) | T-DM1 | |
|
NCT01853748 ° (ATEMPT Trial) |
II | 512 | Stage I HER2-positive BC, adjuvant treatment | T-DM1 vs. Paclitaxel/Trastuzumab | |
| NCT04733118 * (PHERGAIN-2) | II | 393 | HER2-positive untreated eBC | T-DM1 + Pertuzumab + Trastuzumab | |
| NCT03530696 | II | 132 | HER2-positive mBC. Prior treatment with pertuzumab, no more than two lines of therapy for mBC | T-DM1 +/− Palbociclib | |
|
NCT04158947 (HER2BAT) |
II | 130 | HER2-positive BC with central nervous system recurrence/progression during or after an anti-HER2 therapy | T-DM1 +/− Afatinib | |
| NCT04351230 | II | 126 | HER2-positive mBC progressed on treatment with a taxane, trastuzumab and pertuzumab | T-DM1 +/− Abemaciclib | |
| NCT03084939 ° | III | 351 | Chinese patients with HER2-positive mBC who have received prior taxane and trastuzumab. | T-DM1 vs. Capecitabine + Lapatinib | |
|
NCT04740918 * (KATE3) |
III | 350 | HER2-positive and PD-L1 positive mBC pretreated with trastuzumab and taxane | T-DM1+/− Atezolizumab | |
|
NCT03975647 (HER2CLIMB-02) |
III | 460 | HER2- positive mBC; prior treatment with taxane and trastuzumab | T-DM1 +/− Tucatinib | |
|
NCT04457596 (CompassHER2 RDTrial) |
III | 1031 | High risk HER2-positive BC with residual disease after neoadjuvant therapy | T-DM1 +/− Tucatinib |