Trial Outcomes & Findings for Study of ADCT-301 in Patients With Selected Advanced Solid Tumors (NCT NCT03621982)

Participants were enrolled at 9 study centers in 3 countries, including the United States, Belgium, and the United Kingdom, from November 2018 to December 2022.

In part 1, participants were to receive escalating doses of camidanlumab tesirine as monotherapy or escalating doses of camidanlumab tesirine in combination with pembrolizumab, guided by a 3+3 design. The study was terminated prior to enrollment for Part 2 of the study.

Study of ADCT-301 in Patients With Selected Advanced Solid Tumors

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes from baseline in the safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status were reported as TEAEs.

AEs were graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE was graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms, 2 is moderate, 3 is severe, 4 is Life-threatening consequences and 5 is death related to an AE.

A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.

AEs were graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE was graded on a scale of 1 is mild or asymptomatic, 2 is moderate, 3 is severe, 4 is Life-threatening and 5 is death related to an AE.

Dose interruption for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.

Dose reductions for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.

For the dose-escalation of ADCT-301 as monotherapy, DLT is defined as any of the following events like hematologic DLT and non-hematologic DLT which occur during the 21 days following the first study drug administration period of Part 1, except those that are clearly due to underlying disease or extraneous causes. For the dose-escalation of ADCT-301 in combination with pembrolizumab, a DLT is defined as any of the following events ike hematologic DLT and non-hematologic DLT which occur during the 21 days following the first study drug administration period of Part 1, except those that are clearly due to underlying disease or extraneous causes.

The ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The overall response category was derived based on response assessment performed on or before the start of subsequent anti-cancer therapy.

DOR is defined among objective responders (CR or PR) as the time from the earliest date of first response until the first date of either disease progression (based on radiographic or clinical progression at end of treatment \[EOT\]/end of study \[EOS\]) or death due to any cause.

PFS defined as the time between start of treatment and the first documentation of recurrence, progression, or death for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.

OS defined as the time between the start of treatment and death from any cause for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.

The pharmacokinetic (PK) profile included determination of Tmax in serum Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with camidanlumab tesirine in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration is discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

PK profile included AUC0-last of ADCT-301 in Serum total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

The PK profile included AUCinf of ADCT-301 in serum total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

The PK profile included AUCtau ADCT-301 in serum total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

The PK profile included AI of ADCT-301 in serum total antibody and PBD-conjugated antibody. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. AI is the ratio of accumulation of a drug under steady state conditions (i.e., after repeated administration) as compared to a single dose. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

The PK profile included the CL of ADCT-301 in serum total antibody and PBD-conjugated antibody. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

The PK profile included the Thalf of ADCT-301 in serum total antibody and PBD-conjugated antibody. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

The PK profile included determination of Cmax in serum Total antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues. Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.

ADA testing included number of participants with positive pre-dose ADA response, number of participants with post-dose ADA response only, and number of participants with positive ADA response at any time. Collection of ADA was stopped if ADCT-301 administration was discontinued. For participants treated with ADCT-301 in combination with pembrolizumab, unless there was a penultimate observation of positive ADA response, no other collection of ADA data was necessary if ADCT-301 administration was discontinued. Upon consultation with the Sponsor, ADA samples were not collected anymore if ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.