Advanced Solid Tumor, Adult, Melanoma, Metastatic Castrate Resistant Prostate Cancer, Non Small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Cancer
Conditions
Keywords
antibody-drug conjugate (ADC), B7-H3
Brief summary
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.
Interventions
BIOLOGICALvobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Sponsors
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression. * Eastern Cooperative Oncology Group performance status of ≤2 * Life expectancy ≥ 12 weeks for dose escalation phase and ≥ 24 weeks for cohort expansion phase * Measurable disease. Prostate cancer patients with bone only disease are eligible. * Acceptable laboratory parameters and adequate organ reserve. * Dose Escalation Phase: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no therapy with demonstrated clinical benefit is available. Module A Cohort Expansion: * mCRPC that has progressed with one prior line of chemotherapy for metastatic disease and no more than two prior lines of anti-hormonal therapy. * NSCLC: metastatic disease after standard cytotoxic, targeted, and biologic or checkpoint inhibitor therapy. No more than 2 prior lines of chemotherapy. * TNBC: Locally advance or metastatic disease that has progressed following at least one systemic therapy. * SCCHN that has progressed during or following at least one systemic therapy for metastatic or recurrent unresectable disease. No more than 2 prior lines of chemotherapy. * Melanoma that has progressed during or following at least one systemic treatment for unresectable locally advanced or metastatic disease. Patients who are intolerant of or refused standard therapy are eligible.
Exclusion criteria
* Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on MRI, CT or PET within 6 months, or history of leptomeningeal disease or cord compression at the time of enrollment. * Prior treatment with B7-H3 targeted agents for cancer. * Treatment with systemic cancer therapy, biologic agents, or anti-hormonal therapy (mCRPC) within 4 weeks, prior small molecule targeted or kinase inhibitors within 14 days or 5 half-lives, prior radioligand within 6 months * Clinically significant cardiovascular disease. * Clinically significant pulmonary compromise or requirement for supplemental oxygen. * History of clinically-significant cardiovascular disease, including but not limited to pericarditis or pericardial effusion. * Active viral (including confirmed or presumed COVID-19), bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration. * Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction. * Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome. * Major trauma or major surgery within 4 weeks of first study drug administration. * Clinically significant venous insufficiency. * \> Grade 1 peripheral neuropathy. * Evidence of pleural effusion. * Evidence of ascites. * Serum testosterone \>50 ng/dl or \>1.7 nmol/L in mCRPC in Module A Cohort Expansion Phase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | Throughout the study up to 24 months | Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit. |
| Number of Participants With Dose Limiting Toxicities (DLT) | up to 42 days from first dose | Number of participants with severe side effects from study treatment during the DLT evaluation period (6 weels) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) of Vobramitamab Duocarmazine | Every 9 weeks for up to 24 months | PFS is calculated from the first dose date until the date of first documented PD using RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of non-target lesions, or appearance of new lesions. Median PFS and 95% CI is estimated using the Kaplan-Meier method. |
| Median Duration of Response (DoR) of Vobramitamab Duocarmazine | Throughout the study for up to 48 months | Median DoR assessed as the time from the date of initial objective response to the date of first documented PD, per RECIST v1.1, or the date of death from any cause, whichever occurs first. Median DoR and 95% CI is estimated using the Kaplan-Meier method. |
| Median Overall Survival (OS) of Vobramitamab Duocarmazine | Every 9 weeks for up to 24 months | Median OS assessed as the time from the first dose date to the date of death from any cause, using the Kaplan-Meier method for estimating median and confidence interval. . |
| PSA Response Rate | Every 3 weeks up to 24 months | Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later |
| Best PSA Response | Every 3 weeks up to 24 months | For prostate cancer patients, the greatest change from baseline in PSA. |
| Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC) | At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose). | Area under the plasma concentration versus time curve of vobramitamab duocarmazine |
| Best Overall Response (BOR) of Vobramitamab Duocarmazine | Throughout the study for up to 24 months | The best response recorded from the start of the study treatment until the end of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, taking into account any requirement for confirmation of response. Complete response (CR) is defined as disappearance of all target and non-target lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions, and no new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of non-target lesions, or appearance of new lesions. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progression. Not evaluable (NE) is where the response cannot be determined. |
| Mean Maximum Concentration Vobramitamab Duocarmazine ADC | At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3. | Maximum Plasma Concentration of vobramitamab duocarmazine ADC in the bloodstream |
| Mean Maximum Concentration Duocarmycin | At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3. | Maximum Plasma Concentration of vobramitamab duocarmazine ADC in the bloodstream |
| Mean Trough Concentration of Vobramitamab Duocarmazine ADC | At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22). | Average trough plasma concentration of vobramitamab duocarmazine ADC in the bloodstream. |
| Mean Trough Concentration of Duocarmycin | At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22). | Average trough plasma concentration of duocarmycin unconjugated payload in the bloodstream. |
| Number of Participants Who Develop MGC018 Anti-drug Antibodies | Every 3 weeks through end of treatment, up to 24 months | Shifts in MGC018 anti-drug antibodies after treatment with vobramitamab duocarmazine |
| Mean AUC of Duocarmycin | At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose). | Area under the plasma concentration versus time curve of duocarmycin (unconjugated payload) in the bloodstream |
| Objective Response Rate (ORR) of Vobramitamab Duocarmazine | Efficacy evaluations every 9 weeks throughout the study for up to 24 months | The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine |
Countries
Australia, Poland, Spain, United States
Participant flow
Pre-assignment details
Module B of the study was never initiated. There were no participants enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 0.5 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 3 |
| Cohort 2 1.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 6 |
| Cohort 3 2.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 7 |
| Cohort 4 3.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 7 |
| Cohort 5 4.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 6 |
| mCRPC Expansion 3.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 41 |
| NSCLC Expansion 3.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 21 |
| TNBC Expansion 3.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 18 |
| Melanoma Expansion 3.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 21 |
| SCCHN Expansion 3.0 mg/kg IV every 3 weeks
vobramitamab duocarmazine: Anti-B7H3 antibody drug conjugate | 13 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 5 | 4 | 1 | 0 | 34 | 18 | 14 | 19 | 9 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | protocol amendment | 0 | 1 | 3 | 6 | 5 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | study terminated by sponsor | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 3 | 2 | 3 |
Baseline characteristics
| Characteristic | Total | SCCHN Expansion | Melanoma Expansion | TNBC Expansion | NSCLC Expansion | Cohort 1 | mCRPC Expansion | Cohort 5 | Cohort 4 | Cohort 3 | Cohort 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 12.22 | 63.2 years STANDARD_DEVIATION 10.35 | 64.0 years STANDARD_DEVIATION 15.09 | 49.0 years STANDARD_DEVIATION 12.58 | 60.7 years STANDARD_DEVIATION 8.13 | 45.3 years STANDARD_DEVIATION 12.42 | 69.6 years STANDARD_DEVIATION 6.97 | 65.5 years STANDARD_DEVIATION 8.09 | 63.0 years STANDARD_DEVIATION 10.47 | 64.0 years STANDARD_DEVIATION 11.72 | 56.5 years STANDARD_DEVIATION 11.98 |
| Race/Ethnicity, Customized Asian | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 121 Participants | 12 Participants | 19 Participants | 15 Participants | 19 Participants | 3 Participants | 37 Participants | 4 Participants | 4 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Australia | 35 participants | 3 participants | 10 participants | 5 participants | 6 participants | 0 participants | 11 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Poland | 26 participants | 1 participants | 1 participants | 4 participants | 13 participants | 0 participants | 7 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Spain | 22 participants | 9 participants | 4 participants | 7 participants | 0 participants | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment United States | 60 participants | 0 participants | 6 participants | 2 participants | 2 participants | 3 participants | 21 participants | 6 participants | 7 participants | 7 participants | 6 participants |
| Sex: Female, Male Female | 48 Participants | 4 Participants | 5 Participants | 18 Participants | 12 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 95 Participants | 9 Participants | 16 Participants | 0 Participants | 9 Participants | 2 Participants | 41 Participants | 5 Participants | 6 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 5 / 6 | 4 / 7 | 1 / 7 | 0 / 6 | 34 / 41 | 18 / 21 | 14 / 18 | 19 / 21 | 9 / 13 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 7 / 7 | 7 / 7 | 6 / 6 | 41 / 41 | 21 / 21 | 18 / 18 | 21 / 21 | 13 / 13 |
| serious Total, serious adverse events | 1 / 3 | 1 / 6 | 3 / 7 | 2 / 7 | 2 / 6 | 23 / 41 | 10 / 21 | 6 / 18 | 6 / 21 | 5 / 13 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLT)
Number of participants with severe side effects from study treatment during the DLT evaluation period (6 weels)
Time frame: up to 42 days from first dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Cohort 2 | Number of Participants With Dose Limiting Toxicities (DLT) | 1 Participants |
| Cohort 3 | Number of Participants With Dose Limiting Toxicities (DLT) | 1 Participants |
| Cohort 4 | Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Cohort 5 | Number of Participants With Dose Limiting Toxicities (DLT) | 1 Participants |
Primary
Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
Time frame: Throughout the study up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 3 Participants |
| Cohort 2 | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 6 Participants |
| Cohort 3 | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 7 Participants |
| Cohort 4 | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 7 Participants |
| Cohort 5 | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 6 Participants |
| mCRPC Expansion | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 41 Participants |
| NSCLC Expansion | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 21 Participants |
| TNBC Expansion | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 18 Participants |
| Melanoma Expansion | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 21 Participants |
| SCCHN Expansion | Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 | 13 Participants |
Secondary
Best Overall Response (BOR) of Vobramitamab Duocarmazine
The best response recorded from the start of the study treatment until the end of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, taking into account any requirement for confirmation of response. Complete response (CR) is defined as disappearance of all target and non-target lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions, and no new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of non-target lesions, or appearance of new lesions. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progression. Not evaluable (NE) is where the response cannot be determined.
Time frame: Throughout the study for up to 24 months
Population: All participants who received at least one dose of study drug, had baseline measurable or non-measurable disease, and had at least one post-baseline radiographic tumor assessment or discontinued treatment due to clinical progressive disease or death.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 0 Participants |
| Cohort 1 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 2 Participants |
| Cohort 1 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 1 Participants |
| Cohort 1 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 0 Participants |
| Cohort 2 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 3 Participants |
| Cohort 2 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 0 Participants |
| Cohort 2 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 0 Participants |
| Cohort 2 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 3 Participants |
| Cohort 3 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 3 Participants |
| Cohort 3 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 0 Participants |
| Cohort 3 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 0 Participants |
| Cohort 3 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 4 Participants |
| Cohort 4 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 0 Participants |
| Cohort 4 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 4 Participants |
| Cohort 4 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 2 Participants |
| Cohort 4 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 1 Participants |
| Cohort 5 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 1 Participants |
| Cohort 5 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 3 Participants |
| Cohort 5 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 0 Participants |
| Cohort 5 | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 1 Participants |
| mCRPC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 11 Participants |
| mCRPC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 28 Participants |
| mCRPC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 2 Participants |
| mCRPC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 0 Participants |
| NSCLC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 8 Participants |
| NSCLC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 7 Participants |
| NSCLC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 2 Participants |
| NSCLC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 3 Participants |
| TNBC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 0 Participants |
| TNBC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 0 Participants |
| TNBC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 8 Participants |
| TNBC Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 8 Participants |
| Melanoma Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 0 Participants |
| Melanoma Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 1 Participants |
| Melanoma Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 8 Participants |
| Melanoma Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 12 Participants |
| SCCHN Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Progressive Disease | 3 Participants |
| SCCHN Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Partial Response | 1 Participants |
| SCCHN Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Not Evaluated | 2 Participants |
| SCCHN Expansion | Best Overall Response (BOR) of Vobramitamab Duocarmazine | Stable Disease | 7 Participants |
Secondary
Best PSA Response
For prostate cancer patients, the greatest change from baseline in PSA.
Time frame: Every 3 weeks up to 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Best PSA Response | -43.7 ng/mL | Standard Deviation 44.43 |
Secondary
Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC)
Area under the plasma concentration versus time curve of vobramitamab duocarmazine
Time frame: At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose).
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. One participant assigned to Cohort 4 (3.0 mg/kg dose) was actually treated at the Cohort 3 dose of 2.0 mg/kg and is therefore included in Cohort 3 for the purposes of this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC) | 10.6 mcg/mL*day | Standard Deviation 6.54 |
| Cohort 2 | Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC) | 51.5 mcg/mL*day | Standard Deviation 19.2 |
| Cohort 3 | Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC) | 119 mcg/mL*day | Standard Deviation 48.7 |
| Cohort 4 | Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC) | 140 mcg/mL*day | Standard Deviation 34.9 |
| Cohort 5 | Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC) | 227 mcg/mL*day | Standard Deviation 105 |
Secondary
Mean AUC of Duocarmycin
Area under the plasma concentration versus time curve of duocarmycin (unconjugated payload) in the bloodstream
Time frame: At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose).
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. One participant assigned to Cohort 4 (3.0 mg/kg dose) was actually treated at the Cohort 3 dose of 2.0 mg/kg and is therefore included in Cohort 3 for the purposes of this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean AUC of Duocarmycin | 0.0448 ng/mL*day | Standard Deviation 0.023 |
| Cohort 2 | Mean AUC of Duocarmycin | 0.101 ng/mL*day | Standard Deviation 0.0668 |
| Cohort 3 | Mean AUC of Duocarmycin | 0.0512 ng/mL*day | Standard Deviation 0.0454 |
| Cohort 4 | Mean AUC of Duocarmycin | 0.657 ng/mL*day | Standard Deviation 0.0349 |
| Cohort 5 | Mean AUC of Duocarmycin | 0.0268 ng/mL*day | Standard Deviation 0.031 |
Secondary
Mean Maximum Concentration Duocarmycin
Maximum Plasma Concentration of vobramitamab duocarmazine ADC in the bloodstream
Time frame: At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. One participant assigned to Cohort 4 (3.0 mg/kg dose) was actually treated at the Cohort 3 dose of 2.0 mg/kg and is therefore included in Cohort 3 for the purposes of this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Maximum Concentration Duocarmycin | 0.0243 ng/mL | Standard Deviation 0.0225 |
| Cohort 2 | Mean Maximum Concentration Duocarmycin | 0.0274 ng/mL | Standard Deviation 0.016 |
| Cohort 3 | Mean Maximum Concentration Duocarmycin | 0.0512 ng/mL | Standard Deviation 0.0454 |
| Cohort 4 | Mean Maximum Concentration Duocarmycin | 0.657 ng/mL | Standard Deviation 0.0349 |
| Cohort 5 | Mean Maximum Concentration Duocarmycin | 0.0571 ng/mL | Standard Deviation 0.00757 |
Secondary
Mean Maximum Concentration Vobramitamab Duocarmazine ADC
Maximum Plasma Concentration of vobramitamab duocarmazine ADC in the bloodstream
Time frame: At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3.
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. One participant assigned to Cohort 4 (3.0 mg/kg dose) was actually treated at the Cohort 3 dose of 2.0 mg/kg and is therefore included in Cohort 3 for the purposes of this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Maximum Concentration Vobramitamab Duocarmazine ADC | 7.69 mcg/mL | Standard Deviation 1.98 |
| Cohort 2 | Mean Maximum Concentration Vobramitamab Duocarmazine ADC | 23.4 mcg/mL | Standard Deviation 4.08 |
| Cohort 3 | Mean Maximum Concentration Vobramitamab Duocarmazine ADC | 43.4 mcg/mL | Standard Deviation 14 |
| Cohort 4 | Mean Maximum Concentration Vobramitamab Duocarmazine ADC | 59 mcg/mL | Standard Deviation 11 |
| Cohort 5 | Mean Maximum Concentration Vobramitamab Duocarmazine ADC | 76.6 mcg/mL | Standard Deviation 22.4 |
Secondary
Mean Trough Concentration of Duocarmycin
Average trough plasma concentration of duocarmycin unconjugated payload in the bloodstream.
Time frame: At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22).
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. One participant assigned to Cohort 4 (3.0 mg/kg dose) was actually treated at the Cohort 3 dose of 2.0 mg/kg and is therefore included in Cohort 3 for the purposes of this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Trough Concentration of Duocarmycin | 0.000243 ng/mL | Standard Deviation 0.000107 |
| Cohort 2 | Mean Trough Concentration of Duocarmycin | 0.00074 ng/mL | Standard Deviation 0.000532 |
| Cohort 3 | Mean Trough Concentration of Duocarmycin | 0.00226 ng/mL | Standard Deviation 0.00244 |
| Cohort 4 | Mean Trough Concentration of Duocarmycin | 0.00185 ng/mL | Standard Deviation 0.000658 |
| Cohort 5 | Mean Trough Concentration of Duocarmycin | 0.00194 ng/mL | Standard Deviation 0.000973 |
Secondary
Mean Trough Concentration of Vobramitamab Duocarmazine ADC
Average trough plasma concentration of vobramitamab duocarmazine ADC in the bloodstream.
Time frame: At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22).
Population: All participants who received at least one dose of study treatment, date and time of dose administration and relative PK sample collection are known and have sufficient concentration data to derive the PK parameter. One participant assigned to Cohort 4 (3.0 mg/kg dose) was actually treated at the Cohort 3 dose of 2.0 mg/kg and is therefore included in Cohort 3 for the purposes of this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Trough Concentration of Vobramitamab Duocarmazine ADC | 0.00928 mcg/mL | Standard Deviation 0.0129 |
| Cohort 2 | Mean Trough Concentration of Vobramitamab Duocarmazine ADC | 0.0415 mcg/mL | Standard Deviation 0.0415 |
| Cohort 3 | Mean Trough Concentration of Vobramitamab Duocarmazine ADC | 0.123 mcg/mL | Standard Deviation 0.652 |
| Cohort 4 | Mean Trough Concentration of Vobramitamab Duocarmazine ADC | 0.157 mcg/mL | Standard Deviation 0.119 |
| Cohort 5 | Mean Trough Concentration of Vobramitamab Duocarmazine ADC | 0.313 mcg/mL | Standard Deviation 0.323 |
Secondary
Median Duration of Response (DoR) of Vobramitamab Duocarmazine
Median DoR assessed as the time from the date of initial objective response to the date of first documented PD, per RECIST v1.1, or the date of death from any cause, whichever occurs first. Median DoR and 95% CI is estimated using the Kaplan-Meier method.
Time frame: Throughout the study for up to 48 months
Population: Participants who experienced a complete or partial response to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 5 | Median Duration of Response (DoR) of Vobramitamab Duocarmazine | 5.32 months |
| mCRPC Expansion | Median Duration of Response (DoR) of Vobramitamab Duocarmazine | 5.3 months |
| NSCLC Expansion | Median Duration of Response (DoR) of Vobramitamab Duocarmazine | NA months |
| Melanoma Expansion | Median Duration of Response (DoR) of Vobramitamab Duocarmazine | 10.28 months |
| SCCHN Expansion | Median Duration of Response (DoR) of Vobramitamab Duocarmazine | 2.10 months |
Secondary
Median Overall Survival (OS) of Vobramitamab Duocarmazine
Median OS assessed as the time from the first dose date to the date of death from any cause, using the Kaplan-Meier method for estimating median and confidence interval. .
Time frame: Every 9 weeks for up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 3.5 months |
| Cohort 2 | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 5.7 months |
| Cohort 3 | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 13.1 months |
| Cohort 4 | Median Overall Survival (OS) of Vobramitamab Duocarmazine | NA months |
| Cohort 5 | Median Overall Survival (OS) of Vobramitamab Duocarmazine | NA months |
| mCRPC Expansion | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 12.3 months |
| NSCLC Expansion | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 7.0 months |
| TNBC Expansion | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 5.8 months |
| Melanoma Expansion | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 9.4 months |
| SCCHN Expansion | Median Overall Survival (OS) of Vobramitamab Duocarmazine | 5.1 months |
Secondary
Number of Participants Who Develop MGC018 Anti-drug Antibodies
Shifts in MGC018 anti-drug antibodies after treatment with vobramitamab duocarmazine
Time frame: Every 3 weeks through end of treatment, up to 24 months
Population: All participants who received at least one dose of study treatment and have at least one ADA sample sufficient for analysis. There were 3 missing samples.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, positive post baseline | 1 Participants |
| Cohort 1 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, negative post baseline | 2 Participants |
| Cohort 1 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | missing post baseline data | 0 Participants |
| Cohort 2 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, positive post baseline | 1 Participants |
| Cohort 2 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, negative post baseline | 5 Participants |
| Cohort 2 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | missing post baseline data | 0 Participants |
| Cohort 3 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | missing post baseline data | 1 Participants |
| Cohort 3 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, negative post baseline | 6 Participants |
| Cohort 3 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, positive post baseline | 0 Participants |
| Cohort 4 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, positive post baseline | 12 Participants |
| Cohort 4 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, negative post baseline | 102 Participants |
| Cohort 4 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | missing post baseline data | 4 Participants |
| Cohort 5 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | missing post baseline data | 0 Participants |
| Cohort 5 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, positive post baseline | 0 Participants |
| Cohort 5 | Number of Participants Who Develop MGC018 Anti-drug Antibodies | Negative at baseline, negative post baseline | 6 Participants |
Secondary
Objective Response Rate (ORR) of Vobramitamab Duocarmazine
The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine
Time frame: Efficacy evaluations every 9 weeks throughout the study for up to 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 0 percentage of participants |
| Cohort 2 | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 0 percentage of participants |
| Cohort 3 | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 0 percentage of participants |
| Cohort 4 | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 0 percentage of participants |
| Cohort 5 | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 20 percentage of participants |
| mCRPC Expansion | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 4.9 percentage of participants |
| NSCLC Expansion | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 15.0 percentage of participants |
| TNBC Expansion | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 0 percentage of participants |
| Melanoma Expansion | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 4.8 percentage of participants |
| SCCHN Expansion | Objective Response Rate (ORR) of Vobramitamab Duocarmazine | 7.7 percentage of participants |
Secondary
Progression Free Survival (PFS) of Vobramitamab Duocarmazine
PFS is calculated from the first dose date until the date of first documented PD using RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of non-target lesions, or appearance of new lesions. Median PFS and 95% CI is estimated using the Kaplan-Meier method.
Time frame: Every 9 weeks for up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 2.8 months |
| Cohort 2 | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 2.0 months |
| Cohort 3 | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 4.0 months |
| Cohort 4 | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 6.3 months |
| Cohort 5 | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 4.0 months |
| mCRPC Expansion | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 5.5 months |
| NSCLC Expansion | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 4.0 months |
| TNBC Expansion | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 2.4 months |
| Melanoma Expansion | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 3.5 months |
| SCCHN Expansion | Progression Free Survival (PFS) of Vobramitamab Duocarmazine | 3.3 months |
Secondary
PSA Response Rate
Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later
Time frame: Every 3 weeks up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | PSA Response Rate | 18 Participants |