Anal Cancer, Anal Neoplasm, Androgen-Independent Prostatic Cancer, Androgen-Insensitive Prostatic Cancer, Androgen-Resistant Prostatic Cancer, Carcinoma, Squamous Cell of Head and Neck, Castration-Resistant Prostatic Cancer, Head and Neck Squamous Cell Carcinoma, Hormone Refractory Prostatic Cancer, Laryngeal Squamous Cell Carcinoma, Malignant Melanoma, Melanoma, Non-small Cell Carcinoma, Non-small Cell Lung Cancer, Oral Squamous Cell Carcinoma, Small Cell Carcinoma, Small-cell Lung Cancer
Conditions
Brief summary
Study CP-MGC018-03 is an open-label, two-part, Phase 2 study. Part 1 of the study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT). ARAT includes abiraterone, enzalutamide, or apalutamide. Participants may have received up to 1 prior docetaxel-containing regimen, but no other chemotherapy agents. This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks \[Q4W\] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1. Part 2 of the study will enroll participants with locally advanced or metastatic solid tumors. Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab duocarmazine at a dose of 2.7 mg/kg every 4 weeks. Up to 200 participants may be enrolled in Part 2. In both parts, vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered until criteria for treatment discontinuation are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and prostate-specific antigen (PSA) blood tests. Routine examinations and blood tests will be performed and evaluated by the study doctor.
Interventions
BIOLOGICALvobramitamab duocarmazine 2.0 mg (Arm A)
2.0 mg/kg intravenous (IV) every 4 weeks
BIOLOGICALvobramitamab duocarmazine 2.7 mg (Arm B)
2.7 mg.kg IV every 4 weeks
BIOLOGICALvobramitamab duocarmazine
2.7 mg.kg IV every 4 weeks
DRUGAbiraterone
1000 mg once daily
DRUGEnzalutamide
160 mg daily
Sponsors
MacroGenics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Part 1 only: Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features. * Part 2 only: Histologically confirmed SCC or the anus, melanoma, HNSCC, squamous NSCLC, or SCLC. * Part 1 only: Received 1 prior ARAT for metastatic or non-metastatic, castration-sensitive or castration-resistant prostate cancer. A second ARAT regimen of \<60 days used as bridging to lutetium-177 is permitted. Up to 3 total prior lines of therapy for mCRPC are permitted.. * Part 2 only: At least 1 prior line of systemic therapy for unresectable or metastatic disease and no more than 2 prior lines of cytotoxic chemotherapy. Participants with HNSCC or melanoma must have received prior PD-1 or PD-L1 inhibitor for advanced or metastatic disease. * All participants must have ≥ 1 metastatic lesion, according to RECIST 1.1 or PCWG3 criteria, that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment. * All participants must have tumor progression, according to disease-specific criteria, following their most recent anti-cancer therapy. * All participants must have and available archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs * All participants have acceptable physical condition and laboratory values. * All participants of childbearing potential must agree to use highly effective methods of birth control. * All participants must not be pregnant, planning to be pregnant, or breastfeeding.
Exclusion criteria
* Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures. * Part 1 only: Received \>1 prior taxane-containing regimen for prostate cancer. A second taxane regimen of \<60 days used as bridging for lutetium-177 is permitted. * Part 1 only: Received \>3 total prior therapies for mCRPC * Part 1 only: Participants with known BRCA or ATM mutation (germline or somatic) are not eligible unless they received prior treatment with a PARP inhibitor where available, indicated and tolerated. * Another hematologic or solid tumor ≥ stage 1 malignancy that completed surgery, last dose of radiotherapy, or last dose of systemic anti-cancer therapy ≤ 2 years from first dose of study treatment. Participants who had curative therapy for non-melanomatous skin cancer or for localized malignancy are eligible. * Untreated, symptomatic central nervous system (CNS) metastasis. * Prior treatment with any B7-H3 targeted agent for cancer, * Contradictions to the use of corticosteroid treatment * Prior stem cell, tissue, or solid organ transplant. * Part 1 only: Use of products that have published anti-prostate cancer activity or are known to decrease PSA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Six-month Radiographic Progression Free Survival (rPFS) as Determined by the Investigator | Assessed every 8 weeks for six months. Six month data reported. | The landmark analysis for 6 month rPFS rate will occur when all participants on Part 1 have been on study for at least 6 months. |
| Part 2: Objective Response Rate (ORR) Per Investigator Assessment of Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 Criteria | Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months. | The ORR is defined as the percentage of participants in the response evaluable population who achieve a best overall response of complete response (CR) or partial response (PR), per RECIST version 1.1 criterial CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of diameters of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: ORR Per PCWG3 Criteria as Determined by the Investigator | Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months, | To qualify as an objective response, CR and PR require confirmation at least 4 weeks after initial observation of complete response (CR) or partial response (PR). CR + PR = ORR |
| Part 1: Median Duration of Response (DoR) Per PCWG3 Criteria as Determined by the Investigator | Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months. | The DoR will be calculated as the time from the date of initial tumor response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first. |
| Part 1: Mean Best Tumor Size Change Over Time | Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months. | — |
| Part 1: Prostate-specific Cancer Antigen (PSA) Response Rate Per PCWG3 Criteria | Every 4 weeks throughout study participation. Average duration 10 months. | PSA response is defined as a ≥ 50% decline in PSA from baseline with PSA confirmation ≥ 3 weeks after the first documented reduction in PSA of ≥ 50%. |
| Part 1: Time to PSA Progression Per PCWG3 Criteria | Every 4 weeks throughout study participation. Average duration of participation, 10 months. | In participants with a decrease in PSA from baseline, PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥ 3 weeks later. In participants with no decrease in PSA from baseline, PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline value after 12 weeks. Time to PSA progression is defined as the time from the date of randomization to the first PSA progression. |
| Part 1: Duration of PSA Response Per PCWG3 Criteria | Every 4 weeks throughout study participation. Average duration of participation, 10 months. | Duration of PSA response is defined as the time from the date of first documented PSA response to the earliest date of PSA progression. |
| Part 1: Best PSA Percent Change | Every 4 weeks throughout study participation. Average duration of participation, 10 months. | — |
| Part 1: Time to First Symptomatic Skeletal Event (SSE) | Every 4 weeks throughout the study. Average duration of participation, 10 months. | An SSE is defined as any of the following events: new symptomatic pathological fracture, requirement for radiation therapy to relieve bone pain, spinal cord compression, or tumor-related orthopedic surgical intervention. The time to first SSE is defined as the time from the date of randomization to the first occurrence of SSE. |
| Number of Participants With Adverse Event (AEs), Serious AEs (SAEs), and AEs Leading to Study Treatment Discontinuation. | Throughout the study, average duration of participation, 10 months. | — |
| Number of Participants Who Develop Anti-drug Antibodies (ADA) | Every 4 weeks throughout the study, average duration of participation was 10 months. | Participant specimens were evaluated for the presence of ADA beginning a baseline and throughout the study. If at any time during the study, the results show evidence of ADA, they were counted as ADA positive. There was no time-to- event analysis nor by visit analysis of the data. |
| Part 2: Median DoR Per Investigator Assessment of RECIST 1.1 Criteria | Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months. | The DoR will be calculated as the time from the date of initial tumor response (CR or PR) to the date of first documented progressive disease (PD) or death from any cause, whichever occurs first. |
| Part 2: Median Progression Free Survival (PFS) Per Investigator Assessment of RECIST 1.1 Criteria | Every 8 weeks for the first 24 weeks, then every 12 weeks. Average duration of participation, 10 months. | PFS is defined as the time from the date of the first dose to the date of first PD per RECIST 1.1 criteria or death from any cause, whichever occurs first. |
Countries
Australia, Belgium, France, Italy, Poland, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORLiudmila Schafer, M.D.
MacroGenics
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69.1 years STANDARD_DEVIATION 8.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Region of Enrollment Australia | 6 participants |
| Region of Enrollment Belgium | 0 participants |
| Region of Enrollment France | 0 participants |
| Region of Enrollment Italy | 0 participants |
| Region of Enrollment Poland | 0 participants |
| Region of Enrollment South Korea | 2 participants |
| Region of Enrollment Spain | 38 participants |
| Region of Enrollment United Kingdom | 4 participants |
| Region of Enrollment United States | 1 participants |
| Sex/Gender, Customized Female | 0 Participants |
| Sex/Gender, Customized Male | 7 Participants |
| Sex/Gender, Customized Undifferentiated | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 25 / 90 | 21 / 86 | 1 / 3 | 2 / 4 |
| other Total, other adverse events | 89 / 90 | 86 / 86 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 36 / 90 | 44 / 86 | 1 / 3 | 2 / 4 |
Outcome results
None listed