Eligible participants include those with prostate adenocarcinoma (Part 1; prior ARAT therapy permitted) or select squamous/small cell carcinomas (Part 2; 1-2 prior therapies). Key exclusions involve excessive prior treatments, active CNS metastases, B7-H3 therapy history, or contraindications to corticosteroids. Archival tissue and measurable disease are required. Contraception and baseline organ function criteria apply.

Eligible patients must be ≥18 with platinum-refractory SCLC (including EGFR-mutant NSCLC-transformed SCLC), measurable disease (RECIST v1.1), ECOG 0-2, and adequate organ function. Key exclusions: untreated/symptomatic brain metastases, leptomeningeal disease, concurrent malignancies, or significant effusions. Women/men must adhere to strict contraception requirements. Archived/fresh tumor tissue is mandatory unless biopsy is medically unfeasible. Concurrent investigational agents or major surgery within 4 weeks pre-treatment are prohibited.

Female Athymic Nude-Foxn1nu from Envigo (head and neck,triple-negative breast cancer models),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm³,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Prostate cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (QW3).

Male NOG mice from Taconic (prostate cancer model),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm³,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Head and neck cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (Q2W 2).

Female Athymic Nude-Foxn1nu from Envigo (head and neck,triple-negative breast cancer models),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm³,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Triple-negative breast cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (QW2).

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QWx4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,QW1.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 3 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³).MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QWx4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg QWx4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,QW4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³).MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,Q2W4.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 6 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

Human tumor cells (5x10⁶) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm³). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.