Clinical trial NCT06212752: A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)-Japan Extension
Official title: A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Non-small Cell Lung Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-01-19
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to assess the pharmacokinetics (PK) and safety of SC pembrolizumab (+) berahyaluronidase alfa vs intravenous (IV) pembrolizumab, administered with chemotherapy in first line treatment of adult Japanese participants with metastatic non-small cell lung cancer. The primary hypotheses of this study are pembrolizumab (+) berahyaluronidase alfa subcutaneous (SC) is noninferior to pembrolizumab IV with respect to PK parameters.

Detailed description: Japan extension study will require approximately six years which includes one additional year (beyond the global study's last participant last study related contact) from the time the first participant (or their legally acceptable representative) provides informed consent until the last participant's last study related contact to complete.

The Japan extension study will include participants previously enrolled in Japan in the global study for MK-3475A-D77 (NCT05722015) plus the study will continue to enroll participants in Japan until the sample size for participants in Japan reaches approximately 39.

As of Amendment 1 of the supplemental statistical analysis plan (effective date: 23 Aug 2024), patient reported outcomes will no longer be the secondary outcome measures of the study.

Eligibility criteria: The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* Has histologically or cytologically confirmed diagnosis of squamous or non-squamous Non-small Cell Lung Cancer (NSCLC).
* Must provide archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated.
* Has a life expectancy of at least 3 months.

Exclusion Criteria:

* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
* Has received prior systemic anticancer therapy for metastatic NSCLC.
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
* Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicity requiring corticosteroids.
* Has received radiation therapy to the lung (\>30 Gray) within 6 months of start of study intervention.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has an active autoimmune disease that has required systemic treatment in past 2 years.
* Has an active infection requiring systemic therapy.
* Has a history of human immunodeficiency virus (HIV) infection.
* Has a history of Hepatitis B or C.
* Has not adequately recovered from major surgery or has ongoing surgical complications.
* Has a history of allogenic tissue/solid organ transplant.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to ~16 months
Secondary outcomes:
measure: Area Under the Curve (AUC) of Pembrolizumab Measured After the First Dose
timeFrame: At designated time points (Up to ~14 months)
measure: Trough Concentration (Ctrough) of Pembrolizumab Measured at Steady State
timeFrame: At designated time points (Up to ~18 months)
measure: Maximum Serum Concentration (Cmax) of Pembrolizumab Measured After the First Dose
timeFrame: At designated time points (Up to ~28 months)
measure: Trough Concentration (Ctrough) of Pembrolizumab Measured After the First Dose
timeFrame: At designated time points (Up to ~28 months)
measure: Area Under the Curve (AUC) of Pembrolizumab Measured at Steady State
timeFrame: At designated time points (Up to ~28 months)
measure: Maximum Serum Concentration (Cmax) of Pembrolizumab Measured at Steady State
timeFrame: At designated time points (Up to ~28 months)
measure: Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab
timeFrame: At designated time points (Up to ~28 months)
measure: Progression-free Survival (PFS) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to ~59 months
measure: Overall Survival (OS)
timeFrame: Up to ~59 months
measure: Duration of Response (DOR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to ~59 months
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up to~28 months
measure: Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to~25 months
Other outcomes:
Locations:
city: Toyoake
country: Japan
facility: Fujita Health University ( Site 4406)
state: Aichi
city: Kurume
country: Japan
facility: Kurume University Hospital ( Site 4412)
state: Fukuoka
city: Otashi
country: Japan
facility: Gunma Prefectural Cancer Center ( Site 4416)
state: Gunma
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center ( Site 4415)
state: Hokkaido
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center ( Site 4404)
state: Kanagawa
city: Natori
country: Japan
facility: Miyagi Cancer Center ( Site 4401)
state: Miyagi
city: Sendai
country: Japan
facility: Sendai Kousei Hospital ( Site 4400)
state: Miyagi
city: Kurashiki
country: Japan
facility: Kurashiki Central Hospital ( Site 4409)
state: Okayama
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital ( Site 4408)
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital ( Site 4414)
state: Osaka
city: Ina-machi
country: Japan
facility: Saitama Prefectural Cancer Center ( Site 4402)
state: Saitama
city: Nagaizumi-cho,Sunto-gun
country: Japan
facility: Shizuoka Cancer Center ( Site 4405)
state: Shizuoka
city: Utsunomiya
country: Japan
facility: Tochigi Cancer Center ( Site 4417)
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital ( Site 4413)
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center ( Site 4411)
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center ( Site 4410)
city: Osaka
country: Japan
facility: Osaka International Cancer Institute ( Site 4407)
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital ( Site 4403)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: