This multicenter, open-label study will assess the safety and pharmacokinetics of DEDN6526A in patients with metastatic or unresectable melanoma. Cohorts of patients will receive escalating doses of DEDN6526A by intravenous infusion on Day 1 of each 21-day cycle. In the absence of disease progression or unacceptable toxicity, patients may continue to receive DEDN6552A for up to 17 cycles (1 year).

Start Date01 Mar 2012

Sponsor / Collaborator

Genentech, Inc.

100 Clinical Results associated with RG-7636

100 Translational Medicine associated with RG-7636

100 Patents (Medical) associated with RG-7636

Literatures (Medical) associated with RG-7636

01 Jun 2020·Investigational New DrugsQ3 · MEDICINE

Phase I study of the anti-endothelin B receptor antibody-drug conjugate DEDN6526A in patients with metastatic or unresectable cutaneous, mucosal, or uveal melanoma

Q3 · MEDICINE

Article

Author: Infante, Jeffrey R ; Hicks, Rodney ; Meng, Raymond ; Hamid, Omid ; McNeil, Catriona M ; Lemahieu, Vanessa ; Brunstein, Flavia ; Sandhu, Shahneen ; Sanabria, Sandra ; LoRusso, Patricia ; Flanagan, W Michael ; Li, Chunze ; Yeh, Ru-Fang ; Kabbarah, Omar ; Nazzal, Denise ; Patel, Manish R

Background Endothelin B receptor (ET_BR) is involved in melanoma pathogenesis and is overexpressed in metastatic melanoma. The antibody-drug conjugate DEDN6526A targets ET_BR and is comprised of the humanized anti-ET_BR monoclonal antibody conjugated to the anti-mitotic agent monomethyl auristatin E (MMAE). Methods This Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DEDN6526A (0.3-2.8 mg/kg) given every 3 weeks (q3w) in patients with metastatic or unresectable cutaneous, mucosal, or uveal melanoma. Results Fifty-three patients received a median of 6 doses of DEDN6526A (range 1-49). The most common drug-related adverse events (>25% across dose levels) were fatigue, peripheral neuropathy, nausea, diarrhea, alopecia, and chills. Three patients in dose-escalation experienced a dose-limiting toxicity (infusion-related reaction, increased ALT/AST, and drug-induced liver injury). Based on cumulative safety data across all dose levels, the recommended Phase II dose (RP2D) for DEDN6526A was 2.4 mg/kg intravenous (IV) q3w. The pharmacokinetics of antibody-conjugated MMAE and total antibody were dose-proportional at doses ranging from 1.8-2.8 mg/kg. A trend toward faster clearance was observed at doses of 0.3-1.2 mg/kg. There were 6 partial responses (11%) in patients with metastatic cutaneous or mucosal melanoma, and 17 patients (32%) had prolonged stable disease ≥6 months. Responses were independent of BRAF mutation status but did correlate with ET_BR expression. Conclusion DEDN6526A administered at the RP2D of 2.4 mg/kg q3w had an acceptable safety profile and showed evidence of anti-tumor activity in patients with cutaneous, mucosal, and uveal melanoma. ClinicalTrials.gov identifier: NCT01522664.

100 Deals associated with RG-7636

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic melanoma	Phase 1	US	Genentech, Inc.	01 Mar 2012
Metastatic melanoma	Phase 1	AU	Genentech, Inc.	01 Mar 2012
Unresectable Melanoma	Phase 1	US	Genentech, Inc.	01 Mar 2012
Unresectable Melanoma	Phase 1	AU	Genentech, Inc.	01 Mar 2012

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01522664 (Pubmed \| Invest New Drugs) Manual	Phase 1	Uveal Melanoma	53	DEDN6526A	(rdudwsbatv) = DEDN6526A was 2.4 mg/kg intravenous (IV) q3w. xwbasbqamp (iloedoryxp ) View more	Positive	01 Jun 2020
AACR2014	Phase 1	Unresectable Melanoma	28	DEDN6526A	(nblgxpbgzw) = 25% bjcokntndt (sbprrlhucq ) View more	Positive	01 Oct 2014

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