Analysis of Clinical Determinants Driving Safety and Efficacy of Camidanlumab Tesirine (Adct‐301, Cami) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (Chl)

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Introduction: Cami is a humanized anti-CD25 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin with impressive activity in a phase 1 trial (NCT02432235) in heavily pretreated patients (pts) with cHL. Cami's immunological mode of action may have synergistic efficacy with checkpoint inhibitors (CHPi) and could underlie autoimmune toxicities observed in this trial, such as Guillain-Barré Syndrome (GBS)/radiculopathy. Here we report subgroup analyses to identify clinical determinants of antitumor activity, safety, and pharmacokinetic (PK) exposure-response relationships. Methods: R/R cHL pts aged ≥18 years were treated with 5–300 μg/kg Cami every 3 weeks, including dose expansion at 30 and 45 μg/kg. Analyses of response and treatment-emergent adverse events (TEAE) were performed using descriptive statistics. Peak (Cmax) and average (Cavg) concentrations of conjugated antibody in serum were determined using a population PK model and associated with objective response using logistic regression. Results: Overall response rate (ORR) was 73.1% in the study population and 86.5% at 45 μg/kg (n=37; 43.2% complete response). Table 1 presents subgroup analyses of response at 45 μg/kg. Of note, 3 pts improved from partial to complete response after permanent treatment discontinuation. In PK modeling, a significant association of Cmax to objective response was observed for the typical pt (p=3.273 x 10–8; Figure 1); mean predicted probability of Cami response was 0.84 for pts who responded to their most recent therapy vs 0.70 for refractory pts. Autoimmune and neurologic TEAE profiles were comparable between pts with differing prior CHPi exposure. The 5 reported cases of GBS/radiculopathy did not appear related to prior CHPi (≤4 mo: 1 pt [4%]; >4 mo: 1 pt [7%]; none: 2 pts [10%]; 1 pt [20%] who received CHPi but timing information was missing). Updated results will be presented, including response data for the ongoing 30 μg/kg cohort. Conclusions: A difference in Cami response was seen between relapsed vs refractory pts in PK modeling, but response rates were high across all subgroups, suggesting robust antitumor activity across the R/R cHL population. There was a trend for increased ORR in pts with recent prior CHPi exposure, <4 prior therapies, and Stage III cHL. Increased ORR in pts with recent prior CHPi could suggest a possible immunological interaction between Cami and prior CHPi, but it did not appear to increase autoimmune and neurologic TEAEs. Study sponsor: ADC Therapeutics Keywords: Hodgkin lymphoma (HL); immunochemotherapy; immunoconjugates. Disclosures: Collins, G: Consultant Advisory Role: ADC Therapeutics; Research Funding: MSD, Celleron, Celgene, Amgen, ADS Therapeutics; Other Remuneration: Speaker: Roche, Janssen, Gilead; Paid expert testimony: Roche. Horwitz, S: Consultant Advisory Role: ADC Therapeutics, Aileron, Seattle Genetics, Takeda, Kyowa Hakka Kirin, Verastem, Portola, Corvus; Research Funding: Aileron, Celgene, Seattle Genetics, Takeda, Kyowa Hakka Kirin, Verastem, ADC Therapeutics, Spectrum, Forty-Seven; Hamadani, M: Consultant Advisory Role: MedImmune, Jansen, Celgene, Cellerant; Research Funding: Otsuka, Takeda, Sanofi Genzyme, MedImmune, Merck, ADC Therapeutics; Other Remuneration: Speaker bureau: Sanofi, Genzyme. Samaniego, F: Research Funding: ADC Therapeutics; Spira, A: Consultant Advisory Role: AbbVie, AstraZeneca, BMS, Roche; Research Funding: ADC Therapeutics; Caimi, P: Consultant Advisory Role: Genentech, Kite Pharma; Research Funding: ADC Therapeutics; Other Remuneration: Speaker Bureau: Celgene. Davies, A: Consultant Advisory Role: Roche, Acerta Pharma, Karyopharma, Takeda, Celgene; Research Funding: Roche, Acerta Pharma, Gilead, Celgene, GSK, ADC Therapeutics; Other Remuneration: Speaker: Roche, Janssen, Gilead; Paid expert testimony: Roche. Menne, T: Consultant Advisory Role: Amgen, Takeda, Gilead; Research Funding: ADC Therapeutics; Fields, P: Consultant Advisory Role: ADC Therapeutics; Honoraria: Takeda, Roche, MSD; Cruz, H: Employment Leadership Position: ADC Therapeutics; Stock Ownership: ADC Therapeutics; He, S: Employment Leadership Position: ADC Therapeutics; Stock Ownership: ADC Therapeutics; Boni, J: Employment Leadership Position: ADC Therapeutics; Stock Ownership: ADC Therapeutics; Feingold, J: Employment Leadership Position: ADC Therapeutics; Stock Ownership: ADC Therapeutics; Wuerthner, J: Employment Leadership Position: ADC Therapeutics; Stock Ownership: ADC Therapeutics; Radford, J: Research Funding: ADC Therapeutics.