P1, N=43, Terminated, Seagen Inc. | Trial completion date: Nov 2027 --> Dec 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Dec 2023; Study closed due to portfolio prioritization

P1, N=43, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting | N=305 --> 43

For gefitinib treatment, Mice xenotransplanted with H1650 were treated with gefitinib (50mg/kg) daily for 10 days starting from Day 17 post cancer cell inoculation... Our study provides mechanistic insights into ALPP upregulation in cancer cells and establishes FoxO3a as a transcriptional regulator of ALPP. Importantly, our findings have yielded a novel ‘two-hit’ combinational therapeutic strategy with enhanced ALPP targeting for greater efficacy.

Combination therapy with gefitinib and an ALPP antibody conjugated with Monomethylauristatin F resulted in enhanced tumor suppression compared with gefitinib alone. Our findings support a novel combination treatment modality that boosts the efficacy of ALPP-ADC directed therapy.

SGN-ALPV was well tolerated in non-human primates (NHP) and exhibited linear pharmacokinetic characteristics, with a toxicity profile consistent with other vedotin-based ADCs. In summary, differential expression of ALPP and ALPPL2 in the tumor versus normal tissue, antibody specificity, antitumor activity, and tolerability of SGN-ALPV provide a strong rationale for the initiation of a planned first-in-human Phase 1 clinical study.