Inclusion criteria: Adults &ge;18 with isolated distal femur fractures requiring LISS plating, compliant with 1-year MGH follow-ups. Exclusion: Life expectancy <1 year, pre-injury non-ambulatory status, pregnancy, non-LISS implants, bone disorders, neoplasm-related fractures, severe open fractures with vascular damage, or inability to attend follow-ups.

New diagnosis of CD33-expressing AmL, they could not have received prior therapy with HMAs; however, prior low-intensity treatment, such as hydroxyurea for cytoreduction or other low-intensity therapies for preceding myelodysplastic syndrome (MDS), an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, with adequate baseline renal, hepatic, and pulmonary function.

Azacitidine (75 mg/m² subcutaneous/intravenous 7 days) or decitabine (20 mg/m² intravenous 5 days) was administered per institutional standard. On the final day of HMA administration (day 7 of azacitidine treatment and day 5 of decitabine treatment), vadastuximab talirine (10 ug/kg) was administered via slow intravenous push (1-2 mL/min), after infusion of the HMA, as 28-day cycles for up to 4 cycles of treatment.

Eligible participants must have advanced metastatic CRC refractory to &ge;2 prior systemic therapies, ECOG 0-1, and adequate organ function. Key exclusions include prior PBD/IND-based drug exposure, autoimmune/immunodeficiency disorders, IBD history, or recent immunosuppressant use within 14 days prior to treatment. Combination therapy excludes patients with immune-mediated pneumonitis or transplant history.

As of April 2019, 29 patients were enrolled (n=20 in part A and n=9 in part B). All patients experienced at least one treatment-emergent adverse event (TEAE). Two patients (7%) had dose-limiting toxicities of grade 4 thrombocytopenia. All 29 patients discontinued from the study, with study drug being discontinued for 76% of patients due to progressive disease. One death occurred in part A due to gastrointestinal hemorrhage with possible relation to SC-006. Serious TEAEs occurred in 8 patients (28%); these included thrombocytopenia and malignant neoplasm progression in 2 patients (7%) each.

Efficacy endpoints include overall survival (OS) and progression-free survival (PFS) over approximately 2 years, along with pharmacokinetic parameters (Tmax, AUC, T1/2, Cmax, Ctrough) of SC-006 evaluated over 1 year. Tumor response is measured via objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) using RECIST v1.1 criteria.

Eligible participants must have advanced metastatic CRC refractory to &ge;2 prior systemic therapies, ECOG 0-1, and adequate organ function. Key exclusions include prior PBD/IND-based drug exposure, autoimmune/immunodeficiency disorders, IBD history, or recent immunosuppressant use within 14 days prior to treatment. Combination therapy excludes patients with immune-mediated pneumonitis or transplant history.

As of April 2019, 29 patients were enrolled (n=20 in part A and n=9 in part B). All patients experienced at least one treatment-emergent adverse event (TEAE). Two patients (7%) had dose-limiting toxicities of grade 4 thrombocytopenia. All 29 patients discontinued from the study, with study drug being discontinued for 76% of patients due to progressive disease. One death occurred in part A due to gastrointestinal hemorrhage with possible relation to SC-006. Serious TEAEs occurred in 8 patients (28%); these included thrombocytopenia and malignant neoplasm progression in 2 patients (7%) each.

Efficacy endpoints include overall survival (OS) and progression-free survival (PFS) over approximately 2 years, along with pharmacokinetic parameters (Tmax, AUC, T1/2, Cmax, Ctrough) of SC-006 evaluated over 1 year. Tumor response is measured via objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) using RECIST v1.1 criteria.

Eligibility requires CD123-positive AML patients with 1-3 prior regimens (high-risk cases may qualify after 1 regimen), adequate organ function and ECOG 0-1, excluding those with CNS involvement, promyelocytic leukemia, significant pulmonary dysfunction, recent transplants, or recent antileukemia/experimental treatments within 4 weeks (hydroxyurea/6-MP allowed).

Eligibility requires ECOG 0-1 patients with progressive EGFR+ tumors (GBM/CRC/HNSCC/NSCLC/others) refractory to prior therapies (&le;3 cytotoxic lines), measurable disease, and &ge;12-week life expectancy, excluding those with uncontrolled CNS metastases, cardiac dysfunction (NYHA III-IV/EF<40%), active infections (CTCAE&ge;G3), recent major surgery (21 days), or significant effusions/keratitis. Washout periods apply for prior therapies (21 days for most, 5 half-lives for targeted agents).

Eligibility requires ECOG 0-1 patients with PRLR+ advanced tumors (breast/colorectal/adrenocortical/chromophobe RCC in escalation; breast cancer in expansion) refractory to &le;4 cytotoxic lines, excluding prior PBD agents, uncontrolled comorbidities, significant immunotherapy reactions, active gallbladder disease, major liver resection, or ongoing CTCAE >G1 toxicities, with 21-day washout for most prior therapies (14 days for targeted agents).

Locally advanced or metastatic solid tumor types associated with PRLR expression, including breast cancer, colorectal cancer, and adrenocortical carcinoma. Patients had progressed on prior treatment, were not amenable to treatment with curative intent, and had no other therapy options known to provide clinical benefit, or were ineligible for such therapies. Patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate bone marrow, renal, and hepatic function.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO₂ for 24 h and the compounds were added at concentrations of 3x10^-12 - 3x10^-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

Tumor cell lines were maintained in RPMI1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 2 mM L-glutamine and 1 mM sodium pyruvate. 1800 cells per well were seeded in a volume of 180 uL in a 96-well flat bottom polystyrene plate. The cells were allowed to adhere overnight at 37 °C in a CO2 incubator. Ligands were initially formulated in dimethyl sulphoxide, and stocks stored at -80 °C. They were then further formulated at 10× concentration in RPMI1640 medium. 20 uL of diluted samples were added into each treatment well. On each plate, blank wells with no cells, and untreated wells containing cells, were included. Plates were then cultured at 37 °C in a CO2 incubator for 96 h. Cytotoxicity was evaluated in triplicate using a tetrazolium salt-based assay, the MTT assay. After 96 h, the supernatant was removed from each well and 200 uL of a sterile filtered 500 ug mL-1 MTT solution in water added to each well. The plates were then incubated at 37 °C in a CO2 incubator for 4 h. The supernatant was then removed and the formazan crystals formed solubilized by adding 150 uL of dimethyl sulphoxide to each well. The plate was then read on a plate reader at 540 nm, and percentage cell survival calculated as follows: ((mean absorbance treated wells at concentration x - mean absorbance blank wells) ÷ (mean absorbance untreated wells at concentration x - mean absorbance blank wells)) × 100. Data were plotted as concentration in nM vs. % cell survival, and IC50 values for inhibition of cell growth were determined with the GraphPad Prism software using non-linear regression.

Tumor cell lines were maintained in RPMI1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 2 mM L-glutamine and 1 mM sodium pyruvate. 1800 cells per well were seeded in a volume of 180 uL in a 96-well flat bottom polystyrene plate. The cells were allowed to adhere overnight at 37 °C in a CO2 incubator. Ligands were initially formulated in dimethyl sulphoxide, and stocks stored at -80 °C. They were then further formulated at 10× concentration in RPMI1640 medium. 20 uL of diluted samples were added into each treatment well. On each plate, blank wells with no cells, and untreated wells containing cells, were included. Plates were then cultured at 37 °C in a CO2 incubator for 96 h. Cytotoxicity was evaluated in triplicate using a tetrazolium salt-based assay, the MTT assay. After 96 h, the supernatant was removed from each well and 200 uL of a sterile filtered 500 ug mL-1 MTT solution in water added to each well. The plates were then incubated at 37 °C in a CO2 incubator for 4 h. The supernatant was then removed and the formazan crystals formed solubilized by adding 150 uL of dimethyl sulphoxide to each well. The plate was then read on a plate reader at 540 nm, and percentage cell survival calculated as follows: ((mean absorbance treated wells at concentration x - mean absorbance blank wells) ÷ (mean absorbance untreated wells at concentration x - mean absorbance blank wells)) × 100. Data were plotted as concentration in nM vs. % cell survival, and IC50 values for inhibition of cell growth were determined with the GraphPad Prism software using non-linear regression.