Abstract 1030P
Background
CD25+ regulatory T cells (Treg) inhibit tumor-specific T-cell–mediated immune responses and contribute to tumor progression. Cami is an anti-CD25, pyrrolobenzodiazepine (PBD)-based antibody-drug conjugate that depletes CD25+ Tregs, thereby modifying the effector T cells (Teff):Treg intra-tumoral balance. We report preliminary PK and biomarker data of a phase 1 trial of Cami (NCT03621982) in pts with advanced solid tumors.
Methods
This multicenter, open-label, dose-escalation/expansion study is currently enrolling pts (age ≥18 y) with refractory solid tumors. The primary objective is to characterize safety and tolerability of Cami and identify recommended dose(s) and schedule(s). Secondary/exploratory objectives are to evaluate PK, immunogenicity, immunologically-relevant biomarkers in blood and tissues, and preliminary antitumor activity.
Results
PK for total antibody (Ab) and PBD-conjugated Ab appeared dose-related (20–80 μg/kg Q3W/cycle), with substantial inter-patient variability. In cycles 1 and 2, concentrations of CD45+ B and T cells (CD4+, to lesser extent CD8+) gradually increased over days 2 and 4, and declined towards baseline at day 21. Tregs (as % CD3+CD4+ population) decreased in cycle 1, and further decreased in cycle 2, causing a post-treatment increase in Teff:Treg ratio before normalizing towards cycle end and showing dose/cycle dependency. Soluble CD25 in serum followed the increase in CD45+ lymphocytes suggesting an increase of activated lymphocytes. Some pts with paired biopsies showed decreased Tregs and increased Teff:Treg ratio in the local tumor environment.
Conclusions
Preliminary data indicate Cami treatment is associated with clinically-relevant modulation of immune cells, both in circulation and tumor tissue, albeit with substantial inter-patient variability in tumor tissue. Published preclinical data suggest synergism between Cami and checkpoint inhibitors. These results support a potential therapeutic rationale for the treatment of advanced solid tumors with Cami monotherapy or in combination with other immuno-modulating therapies.
Clinical trial identification
NCT03621982.
Editorial acknowledgement
Editorial assistance was provided by Heather St Michael of Fishawack Communications Ltd, UK, contracted by ADC Therapeutics SA.
Legal entity responsible for the study
ADC Therapeutics SA.
Funding
ADC Therapeutics SA.
Disclosure
I. Puzanov: Advisory/Consultancy: Amgen. K. Havenith, K. Anderson, T. Kopotsha: Shareholder/Stockholder/Stock options, Full/Part-time employment: ADC Therapeutics (UK) Ltd. J. Boni: Full/Part-time employment: ADC Therapeutics America, Inc. H.G. Cruz, Y. Le Bruchec, J. Wuerthner: Shareholder/Stockholder/Stock options, Full/Part-time employment: ADC Therapeutics SA. J.C. Bendell: Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Gilead; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Genentech/Roche; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: BMS; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Five Prime; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Lilly; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Merck; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: MedImmune; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Celgene; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Taiho; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Macrogenics; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: GSK; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Novartis; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: OncoMed; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: LEAP; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: TG Therapeutics; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: AstraZeneca; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: BI; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Daiichi Sankyo; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Bayer; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Incyte; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Apexigen; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Array; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Sanofi; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: ARMO; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Ipsen; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Merrimack; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Oncogenex; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: FORMA; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Arch Oncology; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Prelude Therapeutics; Advisory/Consultancy, All honoraria for advisory/consultancy went to institution: Phoenix Bio. 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Research grant/Funding (institution): Innate Pharma; Research grant/Funding (institution): Morphotex; Research grant/Funding (institution): Ongologie; Travel/Accommodation/Expenses: Gilead; Travel/Accommodation/Expenses: Genentech / Roche; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: MedImmune; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Taiho; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: OncoMed; Travel/Accommodation/Expenses: BI; Travel/Accommodation/Expenses: ARMO; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Oncogenex; Travel/Accommodation/Expenses: FORMA. S. Kummar: Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Springworks Therapeutics; Advisory/Consultancy: Genome & Company; Advisory/Consultancy: HarbourBioMed; Advisory/Consultancy: Varian; Advisory/Consultancy: Corvus; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim. K.P. Papadopoulos: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Argule; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Basilia; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Anheart; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MedImmune; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Peleton Therapeutics; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): ArQule; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Calithera Biosciences; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Curegenix; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Incyte; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): F-Star Delta Limited; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Jounce; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): ADC Therapeutics; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Tempest Therapeutics; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Linnaeus Therapeutics 3D Medicines; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Formation Biologics; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): EMD Serono; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Syros Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Mersana; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MabSpace Biosciences; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Jounce Therapeutics. P. LoRusso: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Agios (DSMB); Advisory/Consultancy: Five Prime (DSMB); Advisory/Consultancy: GenMab; Advisory/Consultancy: Haolzyme (DSMB); Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: Genentech; Advisory/Consultancy: CytomX; Advisory/Consultancy: Takeda; Advisory/Consultancy: Sotio; Advisory/Consultancy: Cybrexa; Advisory/Consultancy: Agenus (2018-20); Advisory/Consultancy: Tyme (DSMB); Advisory/Consultancy: IQVIA; Advisory/Consultancy: TRIGR; Advisory/Consultancy: Pfizer; Advisory/Consultancy: I-MAB; Advisory/Consultancy: ImmunoMet; Advisory/Consultancy: GSK; Advisory/Consultancy: Black Diamond; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Shattuck; Advisory/Consultancy: Astellas; Advisory/Consultancy: Salarius; Advisory/Consultancy: Silverback; Advisory/Consultancy: MacroGenics; Advisory/Consultancy: Kyowa Kirin Pharmaceutical Development; Advisory/Consultancy: Kineta, Inc.; Advisory/Consultancy: Zentalis Pharmaceuticals; Advisory/Consultancy: Molecular Templates; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): ADC Therapeutics; Research grant/Funding (institution): ALX Oncology, Inc.; Research grant/Funding (institution): Astellas Pharma US, Inc.; Research grant/Funding (institution): Astex Pharmaceuticals, Inc.; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer Healthcare Pharmaceuticals, Inc.; Research grant/Funding (institution): Boehringer Ingelheim Pharmaceuticals, Inc.; Research grant/Funding (institution): Bristol-Myers Squibb Research & Development; Research grant/Funding (institution): Corvus Pharmaceuticals, Inc.; Research grant/Funding (institution): CytomX Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai Pharmaceuticals; Research grant/Funding (institution): Eli Lilly & Company; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Five Prime Therapeutics, Inc.; Research grant/Funding (institution): Rapt Therapeutics; Research grant/Funding (institution): F-Star Delta Limited; Research grant/Funding (institution): Genentech, Inc.; Research grant/Funding (institution): Genmab, Inc.; Research grant/Funding (institution): Incyte Corporation; Linnaeus Therapeutics, Inc.; Research grant/Funding (institution): MedImmune, Inc.; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Moderna Therapeutics, Inc.; Research grant/Funding (institution): NextCure, Inc.; Research grant/Funding (institution): Novartis Pharmaceuticals; Research grant/Funding (institution): Radius Pharmaceuticals; Sotio; Research grant/Funding (institution): Stemline Therapeutics, Inc.; Research grant/Funding (institution): Tesaro, Inc.