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

NCT03760081 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 1650-CL-0201
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study was to establish the recommended phase 2 dose (RP2D) of ASP1650 (Safety Lead-in Phase), as well as, evaluate the efficacy of ASP1650 as measured by confirmed objective response rate (ORR) (phase 2) in participants with incurable platinum refractory germ cell tumors. This study also evaluated the following efficacy measures for confirmed objective response rate (ORR); clinical benefit rate (CBR); duration of response (DOR); and progression-free survival (PFS); as well as safety and tolerability; the effect of ASP1650 on changes in serum beta human chorionic gonadotropin (βhCG) and alpha-fetoprotein (AFP); and the pharmacokinetics of ASP1650.

Conditions

Incurable Platinum Refractory Germ Cell Tumors; Tumors

Keywords

Incurable Platinum Refractory Germ Cell Tumors; ASP1650

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) of ASP1650

  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.

  Up to 28 days

• Percentage of Participants With Confirmed Objective Response by Modified RECIST v1.1

  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.

  From randomization until confirmed CR or confirmed PR, whichever occurred first (up to 26.57 weeks)

Secondary Outcomes (12)

• Percentage of Participants With Confirmed Objective Response by RECIST v1.1

  From randomization until confirmed CR or confirmed PR, whichever occurred first (up to 26.57 weeks)

• Percentage of Participants With Clinical Benefit by Modified RECIST v1.1 and RECIST v1.1

  From randomization until confirmed CR, confirmed PR, or durable SD whichever occurred first (up to 26.57 weeks)

• Duration of Response (DOR) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2

  From randomization until confirmed CR or confirmed PR whichever occurred first (up to 26.57 weeks)

• Progression-Free Survival (PFS) by Modified RECIST v1.1 and RECIST v1.1 for Dose Level 2

  From the date of first dose until the date of disease progression, or until death due to any cause (up to 26.57 weeks)

• Number of Participants With Adverse Events (AEs)

  From first dose of study drug up to 30 days after the last dose of study drug (up to 41.14 weeks)

Study Arms (2)

ASP1650, Dose Level 1

EXPERIMENTAL

Participants received ASP1650 dose level 1 as intravenous infusion, every two weeks (Q2W) starting on Cycle 1 Day 1(C1D1) for up to a maximum of 12 cycles, or until disease progression, toxicity requiring study treatment cessation, start of another anticancer treatment, or until study discontinuation criteria was met, whichever occurred earlier. Duration of each treatment cycle was 14 days.

Drug: ASP1650

ASP1650, Dose Level 2

EXPERIMENTAL

Participants received ASP1650 dose level 2 as intravenous infusion, Q2W starting on C1D1 for up to a maximum of 12 cycles or until study discontinuation criteria as met, whichever occurred earlier. Duration of each treatment cycle was 14 days.

Drug: ASP1650

Interventions

ASP1650 DRUG

Participants received ASP1650 dose level 1 or dose level 2 as intravenous infusion, Q2W starting on C1D1 for up to a maximum of 12 cycles or until study discontinuation criterion was met, whichever occurred earlier. Duration of each treatment cycle was 14 days.

ASP1650, Dose Level 1; ASP1650, Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
• Subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
• A male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study treatment administration.
• Subject agrees not to participate in another interventional study while receiving study drug in present study.
• Disease Specific Criteria:
• Subject has histological evidence of germ cell tumor.
• Subject must have a germ cell tumor that is not amenable to cure with either surgery or chemotherapy.
• Subjects with seminoma and non-seminoma are eligible.
• Subject must have received initial cisplatin based combination chemotherapy AND demonstrated progression following at least 1 salvage regimen for advanced germ cell neoplasm (including relapsed primary mediastinal nonseminomatous germ cell tumor).
• Initial cisplatin based combination therapy includes bleomycin-etoposide-cisplatin, cisplatin-etoposide, etoposide-ifosfamide-cisplatin or similar regimens.
• "Salvage" regimens include high dose chemotherapy, paclitaxel-ifosfamide-cisplatin, vinblastine-ifosfamide cisplatin or similar regimens
• "Failure" of prior therapy is defined as: A \> 25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy, which are not amenable to surgical resection; OR the presence of new tumor that are not amenable to surgical resection; OR an increase in alpha-fetoprotein (AFP) or beta human chorionic gonadotropin (βhCG) (≥ 50% increase in 2 separate samples collected at least 1 week apart are required if rising tumor markers are the only evidence of failure). NOTE: Subjects with clinically growing teratoma (enlarging mature teratoma arising during or after chemotherapy for a non seminomatous germ-cell tumor and with normal serum levels of AFP and βhCG) should undergo surgical resection if feasible.
• Subjects with late relapse (\> 2 years) not amenable to resection are eligible.
• Subjects must have evidence of recurrent or metastatic carcinoma by 1 or more of the following:
• Subject has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.

You may not qualify if:

• Prohibited Treatment or Therapies:
• Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) is eligible. Subject who received systemic steroids for asymptomatic central nervous system (CNS) metastases within 14 days prior to first dose of study treatment is eligible.
• Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
• Subject has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse event (AE) due to monoclonal antibody (mAb) agents administered more than 4 weeks earlier.
• Subject has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 2 or at baseline) from AEs due to a previously administered agent.
• Medical History or Concurrent Disease:
• Subject has prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies requiring permanent discontinuation.
• Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
• Subject has an active human immunodeficiency virus (HIV) infection or known active hepatitis B (HBsAg) or C infection. Subjects with well-controlled HIV infections (i.e., without detectable viral load) are eligible. For subjects who are negative for HBsAg, but hepatitis B core antibody (HBcAb) positive, an HBsAg deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded. Subjects with positive serology but negative hepatitis C virus (HCV) ribonucleic acid (RNA) test results are eligible.
• Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose of study treatment.
• Subject has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subject with asymptomatic CNS metastases is eligible.
• Subject has had a major surgical procedure and has not completely recovered within 28 days prior to the first dose of study treatment.
• Subject has psychiatric illness or social situations that would preclude study compliance.
• Subject has another malignancy for which treatment is required. Subject with negligible risk of metastasis or death is eligible (e.g., basal or squamous cell skin cancer, localized prostate cancer treated with curative intent or incidental prostate cancer T1-T2a, Gleeson ≤ 3 + 4, PSA ≤ 0.5 and who are undergoing active surveillance).
• Subject has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (3)

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Abramson Cancer Center University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Adra N, Vaughn DJ, Einhorn LH, Hanna NH, Funt SA, Rosales M, Arozullah A, Feldman DR. A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors. Invest New Drugs. 2022 Oct;40(5):1087-1094. doi: 10.1007/s10637-022-01276-w. Epub 2022 Jun 27.

  PMID: 35759134 DERIVED

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website.

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: November 30, 2018
• Study Start: March 19, 2019
• Primary Completion: October 16, 2020
• Study Completion: October 16, 2020
• Last Updated: November 13, 2024
• Results First Posted: November 10, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)