Trial Outcomes & Findings for A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors (NCT NCT03760081)

Participants were enrolled at 3 sites in the United States.

Adult male participants with incurable platinum refractory germ cell tumors for whom no standard of care treatment exists or who are ineligible to receive available standard of care treatment based on investigator's clinical judgment, who met all inclusion criteria and met none of the exclusion criteria were enrolled in this study. A total of 23 participants entered screening process and out of which 4 participants failed screened process.

A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors

The RP2D was determined via dose limiting toxicity (DLT) assessment by dose evaluation committee (DEC). DLT was evaluated according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Confirmed objective response was defined as the confirmed completed response (CR) or confirmed partial response (PR), as confirmed by investigator based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Per modified RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Both Alpha-Fetoprotein (AFP) and Beta Human Chorionic Gonadotropin (beta-HCG) values were below the ULN. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. No increase ≥ 50% in 2 samples at least 1 week apart compared to nadir values for both AFP and beta-HCG.

Confirmed objective response was defined as the confirmed CR or PR, as confirmed by investigator based on RECIST v1.1. Per RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Clinical benefit: defined as best overall response of confirmed CR, confirmed PR, or durable stable disease (SD) as confirmed by investigator based on modified RECIST v1.1 and RECIST v1.1. Per RECIST v1.1 and modified RECIST V1.1, CR: disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. PR:at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference smallest sum diameters while on study. Durable SD: SD maintained for at least 12 weeks. Additionally, per modified RECIST v1.1, CR also included AFP and beta-HCG values below ULN. PR also included no increase ≥ 50% in 2 samples at least 1 week apart compared to nadir values both for AFP and beta-HCG.

DOR was defined as the time from the date of the first confirmed response CR or confirmed PR (whichever was first recorded) as confirmed by investigator based on modified RECIST 1.1 and RECIST v1.1 to the date of disease progression or date of censoring, whichever was earlier. If a participant had not progressed, participant was censored at the date of last disease assessment or at the date of first confirmed CR/PR if no post-baseline disease assessment was available. DOR (in days) was calculated as: (Date of documented progressive disease \[PD\], death, or censoring) minus (Date of the first CR/PR which was subsequently confirmed) +1. Duration of response was planned to summarized only for participants receiving dose level 2 in phase 2.

PFS was defined as the time from the date of first dose until the date of disease progression, or until death due to any cause. If a participant had neither progressed nor died, the participant was censored at the date of last disease as confirmed by investigator based on modified RECIST v1.1 and RECIST v1.1. The distribution of PFS was planned to be summarized only for participants receiving dose level 2 using Kaplan-Meier methodology. Per modified RECIST v1.1 and RECIST v1.1, Progressive disease (PD): appearance of one or more new lesions or at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must be an absolute increase of at least 5 mm. Additionally per modified RECIST v1.1, PD was increase ≥ 50% in serum tumor markers AFP or beta-hCG in 2 samples at least 1 week apart compared to nadir values.

An AE was defined as any untoward medical occurrence in a participant administered with an Investigational Product (IP) which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign including abnormal laboratory finding/test result or other safety assessment, symptom, or disease temporally associated with use of IP whether or not considered related to IP. A treatment-emergent adverse event (TEAE) was defined as an AE with onset at any time from first dosing until last scheduled procedure. AEs were considered serious (SAEs) if AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, birth defect, or required inpatient hospitalization or led to prolongation of hospitalization.

Number of participants with shifts from baseline to post baseline in ECOG PS levels were reported. ECOG has 6 levels (0-5). Level 0 is fully active, able to carry on all pre-disease performance without restriction; Level 1 is restricted in physically strenuous activity but ambulatory ad able to carry out work of a light or sedentary nature, e.g. light house work, office work; Level 2 is ambulatory and capable of all self care but unable to carry out any work activities; up and about more than 50% of waking hours; Level 3 is capable of only limited self care; confined to bed or chair more than 50% of waking hours; Level 4 is completely disabled; cannot carry on any self care; totally confined to bed or chair); and Level 5 is dead.

Blood was drawn for the measurement of serum βhCG at day 1 of every cycle (14 day cycle) to align with imaging assessment until the participant develops radiological disease progression per RECIST v1.1 evaluation or starts other systemic anticancer treatment. To evaluate the effect of ASP1650 on changes in serum βhCG, disease response was derived for participants with elevated serum tumor markers at baseline using CR, PR and SD.

Blood was drawn for the measurement of serum AFP at day 1 of every cycle (14 day cycle) to align with imaging assessment until the participant develops radiological disease progression per RECIST v1.1 evaluation or starts other systemic anticancer treatment. To evaluate the effect of ASP1650 on changes in serum AFP, disease response was derived for participants with elevated serum tumor markers at baseline using CR, PR and SD.

AUC336 was derived from the Pharmacokinetic (PK) plasma samples collected. Duration of each cycle was 14 days.

Cmax was derived from the PK plasma samples collected. Duration of each cycle was 14 days.

Tmax was derived from the PK plasma samples collected. Duration of each cycle was 14 days.

Ctrough was derived from the PK plasma samples collected. Duration of each cycle was 14 days.