P1, N=260, Active, not recruiting, ADC Therapeutics S.A. | Recruiting --> Active, not recruiting

P2, N=240, Active, not recruiting, BioAtla, Inc. | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jun 2024 --> Dec 2024

We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific anti-tumor activity in a MES cell line-derived xenograft...Several plasma membrane proteins are being developed as immunotherapeutic targets in this disease. Here we define which cell surface proteins are susceptible to epigenetically regulated downregulation during an adrenergic to mesenchymal cell state switch and propose immunotherapeutic strategies to anticipate and circumvent acquired immunotherapeutic resistance.

So far, the antibody-drug conjugates have struggled from efficacy problems, with modest effects at best, leading many to be discontinued for melanoma. At the same time, conjugates such as AMT-253, targeting melanoma cell adhesion molecule, and mecbotamab vedotin  targeting AXL receptor tyrosine kinase, are among the most exciting for melanoma treatment in the future.

P1/2, N=300, Recruiting, BioAtla, Inc. | N=120 --> 300

P1, N=260, Recruiting, ADC Therapeutics S.A. | N=196 --> 260

P1, N=196, Recruiting, ADC Therapeutics S.A. | Phase classification: P1b --> P1

No abstract available

P1b, N=196, Recruiting, ADC Therapeutics S.A. | N=66 --> 196

No abstract available

To enroll, patients must have experienced failure of an approved programmed death1/ligand-1(PD-1/L1) treatment, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) inhibitor (either monotherapy or in combination with another therapy such as ipilimumab). Treatment failure is defined as disease progression on a PD-1/L1, EGFR, or ALK inhibitor, or discontinuation of a PD-1/L1, EGFR, or ALK inhibitor due to an adverse event. Enrollment completion is anticipated in 2023.

To enroll, patients must have experienced failure of an approved programmed death1/ligand-1(PD-1/L1) treatment, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) inhibitor (either monotherapy or in combination with another therapy such as ipilimumab). Treatment failure is defined as disease progression on a PD-1/L1, EGFR, or ALK inhibitor, or discontinuation of a PD-1/L1, EGFR, or ALK inhibitor due to an adverse event. Enrollment completion is anticipated in 2023.

Trial Design Study BA3011-001 is an ongoing multi-center, open-label phase I/II first-in-human trial designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3011 alone and in combination with the PD-1 inhibitor nivolumab in adult and adolescent patients 12 years and older with advanced solid tumors. Enrollment in phase II part 2 is expected to commence in January 2023. Legal entity responsible for the study BioAtla, Inc.

The purpose of this study was to test a suboptimal single dose of mipasetamab uzoptirine (ADCT-601), an ADC targeting the AXL protein, in combination with ultrasound-induced cavitation in a preclinical mouse model of renal cancer...This was demonstrated for a suboptimal ADC dose, indicating that ultrasound-mediated drug delivery could be used to reduce the administered dose while preserving therapeutic efficacy. These preclinical data warrant further evaluation of this promising combination in the clinic.

Doxorubicin (doxo) remains the standard of care for patients with advanced soft tissue sarcoma (STS), even though response rates to doxo are only around 14% to 18%. One model was found negative for AXL on experimental passage and did not respond to EnaV. This study provides a preclinical rationale for the evaluation of AXL-targeting ADCs in the treatment of AXL-expressing sarcomas.

P1b, N=66, Recruiting, ADC Therapeutics S.A. | Not yet recruiting --> Recruiting

P1b, N=66, Not yet recruiting, ADC Therapeutics S.A.

Notably, ADCT-601 had antitumor activity in a monomethyl auristatin E-resistant lung-cancer model and synergized with the PARP inhibitor olaparib in a BRCA1-mutated ovarian cancer model. ADCT-601 was well tolerated at doses of up to 6 mg/kg and showed excellent stability in vivo. These preclinical results warrant further evaluation of ADCT-601 in the clinic.

This study demonstrated that ADCT-601 induced a potent and specific in vitro and in-vivo anti-tumor activities in AXL expressing ACC models and suggests further development of ADCT-601 in biomarker driven clinical trials.

P1/2, N=306, Completed, Genmab | Active, not recruiting --> Completed | Trial primary completion date: Aug 2021 --> Nov 2021

Based on preliminary efficacy and safety results from this study, the benefit-risk profile of BA3011 monotherapy appears to be favorable in subjects with sarcoma. No clinically meaningful on-target toxicity was observed. In Phase 1 sarcoma subjects, evidence of antitumor activity was observed, with higher AXL tumor membrane expression correlating with response.

Here we show that enapotamab vedotin (EnaV), an antibody-drug conjugate (ADC) targeting AXL, effectively targets tumors that display insensitivity to immunotherapy or tumor-specific T cells in several melanoma and lung cancer models...Combining EnaV with tumor-specific T cells proved superior to either treatment alone in models of melanoma and lung cancer and induced ICB benefit in models otherwise insensitive to anti-PD-1 treatment. Our findings indicate that targeting AXL-expressing, immunotherapy-resistant tumors with EnaV causes an immune-stimulating tumor microenvironment and enhances sensitivity to ICB, warranting further investigation of this treatment combination.

P1, N=75, Suspended, ADC Therapeutics S.A. | Recruiting --> Suspended