Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Melanoma

Squamous Cell Carcinoma of Head and Neck

Neoplasms by Histologic Type

Skin Diseases

Neoplasms, Glandular and Epithelial

Breast Diseases

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Mitoguazone

vobramitamab duocarmazine

Ashley Ward, M.D.

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.

Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.

MGC018 With or Without MGA012 in Advanced Solid Tumors

A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors

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.

Maximum tolerated or maximum administered dose of vobramitamab duocarmazine

The best response recorded from the start of the study treatment until the end of treatment with vobramitamab duocarmazine, taking into account any requirement for confirmation of response.

The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine

Efficacy assessed as the first dose date to the date of first documented progression using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first.

Efficacy assessed as the time from the date of initial objective response to the date of first documented progression RECIST v1.1, or the date of death from any cause, whichever occurs first.

Efficacy assessed as the time from the first dose date to the date of death from any cause.

Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later

For prostate cancer patients, the greatest change from baseline in PSA.

Area under the plasma concentration versus time curve of vobramitamab duocarmazine

Maximum Plasma Concentration of vobramitamab duocarmazine

Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine

Trough plasma concentration of vobramitamab duocarmazine

Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab

Apparent volume of distribution at steady state of vobramitamab duocarmazine

Terminal half life of vobramitamab duocarmazine

Percent of patients with anti-drug antibodies against vobramitamab duocarmazine

MacroGenics

Digestive System Diseases

Rare Diseases

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Anus Neoplasms

Prostatic Neoplasms, Castration-Resistant

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neoplasms, Squamous Cell

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Small Cell Lung Cancer

Oral Squamous Cell Carcinoma

Anal Cancer

Neuroendocrine Tumor

Neuroepithelioma

vobramitamab duocarmazine 2.0 mg (Arm A)

vobramitamab duocarmazine 2.7 mg (Arm B)

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 squamous cell carcinoma (SCC) of the anus, melanoma, head and neck squamous cell carcinoma (HNSCC), squamous non-small cell lung carcinoma (NSCLC), and small cell lung carcinoma (SCLC). Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab docarmazine 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 for up to 26 cycles, approximately 2 years, 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.

A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors

A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

The rPFS is defined as the time from the date of randomization to the date of first documented progressive disease (PD) per Prostate Cancer Working Group 3 (PCWG3) or death from any cause, whichever occurs first. Three arms will be compared: Arm A, Arm B, and control.

The ORR is defined as the percentage of participants in the response evaluable poplaiton who achieve a best overall response of conplete 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.

The number of participants experiencing a complete response (CR) or partial response (PR) to treatment.

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.

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%.

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.

Duration of PSA response is defined as the time from the date of first documented PSA response to the earliest date of PSA progression.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MGC018 With or Without MGA012 in Advanced Solid Tumors	NCT03729596	Squamous Cell C... Triple Negative... Melanoma Advanced Solid ... Metastatic Cast... Non Small Cell ...	vobramitamab du...	18 Years -	MacroGenics
A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors	NCT05551117	Castration-Resi... Androgen-Indepe... Androgen-Insens... Androgen-Resist... Hormone Refract... Anal Cancer Anal Neoplasm Carcinoma, Squa... Head and Neck S... Laryngeal Squam... Oral Squamous C... Malignant Melan... Melanoma Non-small Cell ... Non-small Cell ... Small-cell Lung... Small Cell Carc...	vobramitamab du... vobramitamab du... vobramitamab du...	18 Years -	MacroGenics
A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors	NCT05551117	Castration-Resi... Androgen-Indepe... Androgen-Insens... Androgen-Resist... Hormone Refract... Anal Cancer Anal Neoplasm Carcinoma, Squa... Head and Neck S... Laryngeal Squam... Oral Squamous C... Malignant Melan... Melanoma Non-small Cell ... Non-small Cell ... Small-cell Lung... Small Cell Carc...	vobramitamab du... vobramitamab du... vobramitamab du...	18 Years -	MacroGenics
MGC018 With or Without MGA012 in Advanced Solid Tumors	NCT03729596	Squamous Cell C... Triple Negative... Melanoma Advanced Solid ... Metastatic Cast... Non Small Cell ...	vobramitamab du...	18 Years -	MacroGenics

Spots Global Cancer Trial Database for vobramitamab duocarmazine