Advanced or Metastatic Solid Tumors, Colo-rectal Cancer, Gastric Cancer, Ovarian Cancer
Conditions
Keywords
Advanced Cancer, Metastatic Cancer, NC410, Solid Tumor, Immunotherapy, PK, Ovarian Cancer, Gastric Cancer, Colo-rectal Cancer
Brief summary
This research study is studying a new drug, NC410, as a possible treatment for advanced or metastatic solid tumors.
Interventions
DRUGNC410
NC410 is an experimental antibody drug that may make the immune response more active against cancer
Sponsors
NextCure, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women aged 18 or older. * Willingness to provide written informed consent for the study. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. * Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. * Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. Note: There is no limit to the number of prior treatment regimens. * Presence of measurable disease based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measurable unless there has been demonstrated progression in the lesion. * After dose escalation, subject must be willing to undergo pretreatment and on-treatment tumor biopsies (core or excisional). Note: A baseline biopsy obtained for other purposes (i.e., not an NC410-01 study procedure) before signing consent may be utilized if the subject has not had any intervening systemic therapy from the time of the biopsy to the start of treatment with the medical monitor's approval. * Female subjects of childbearing potential (defined as women who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not postmenopausal, defined as ≥ 12 months of amenorrhea) must have a negative serum pregnancy test at screening. All female and male subjects of childbearing potential must agree to take appropriate precautions to avoid pregnancy or fathering children (with at least 99% certainty) from screening through 60 days after the last dose of study drug.
Exclusion criteria
* Inability to comprehend or unwilling to sign the Informed Consent Form. * Screening laboratory values of: 1. Absolute neutrophil count \< 1.5 × 10\^9/L 2. Platelets \< 100 × 10\^9/L 3. Hemoglobin \< 9 g/dL or \< 5.6 mmol/L 4. Serum creatinine \> 1.5 × institutional upper limit of normal (ULN) 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 × ULN 6. Total bilirubin ≥ 1.5 × ULN unless conjugated bilirubin ≤ ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then direct bilirubin must be \< 40% of total bilirubin. 7. International normalized ratio (INR) or prothrombin time (PT) \> 1.5 × ULN 8. Activated partial thromboplastin time (aPTT) \> 1.5 × ULN * Transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before the first administration of study drug. * Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study drug: 1. ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis because of a treatment. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with medical monitor approval. Note: Bisphosphonates and denosumab are permitted medications. 2. ≤ 28 days for prior immunotherapy or persistence of active cellular therapy (e.g., chimeric antigen receptor T cell therapy; other cellular therapies must be discussed with the medical monitor to determine eligibility). 3. ≤ 28 days for a prior monoclonal antibody used for anticancer therapy except for denosumab. 4. ≤ 7 days for immune-suppressive-based treatment for any reason. Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted. Note: The use of physiologic corticosteroid replacement therapy may be approved after consultation with the medical monitor. 5. ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices. For investigational agents with long half-lives (e.g., \> 5 days), enrollment before the fifth half-life requires medical monitor approval. * Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting therapy. Note: Subjects with stable chronic conditions (≤ Grade 2) not expected to resolve (such as neuropathy and alopecia) are exceptions and may enroll. Note: Subjects with a history of any grade immune-related ocular AE (e.g., episcleritis, scleritis, uveitis) will be excluded. * Receipt of a live vaccine within 30 days of planned start of study therapy. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. * Active autoimmune disease that required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Subjects who have not required systemic treatment in the past 2 years may be eligible with approval of the medical monitor. Note: Subjects with hyper/ hypothyroidism are eligible to participate. Note: Replacement and symptomatic therapies (e.g., levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered a form of systemic immune suppressive therapy and are allowed. * Known active CNS metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days before the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases or CNS edema, and have not required steroids for at least 7 days before the first dose of study drug. * Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry apart from cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the subject has been disease-free for \> 1 year, after treatment with curative intent. * Evidence of active, noninfectious pneumonitis or history of interstitial lung disease. * History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. * Active infection requiring systemic therapy. * Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation. HBV-DNA and HCV-RNA must be undetectable. Subjects cannot be positive for HBV-DNA, HCV-RNA, hepatitis B surface antigen, or anti-hepatitis B core antibody. Note: Subjects with no prior history of hepatitis B infection who have been vaccinated against hepatitis B and who have a positive antibody against hepatitis B surface antigen test as the only evidence of prior exposure may participate in the study. * Known history of HIV (HIV 1 or HIV 2 antibodies). * Known allergy or reaction to any component of study drug or formulation components. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 60 days after the last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | From enrollment through up to 90 days after end of treatment, an average of 1 year | Number of Participants With Treatment-emergent Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | Approximately 1 year | To assess antitumor activity/efficacy by evaluating duration of response (DoR), defined as the time from the first documented complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Modified Response Evaluation Criteria in Solid Tumors to the first documented progressive disease or death due to any cause, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: CompleteResponse (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions . |
| Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Approximately 1 year | To assess antitumor activity/efficacy by evaluating disease control rate (DCR), defined as the proportion of participants in whom a documented complete response, partial response, or stable disease is observed as the best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
| Maximum Plasma Concentration (Cmax) of NC410 | Days 1, 2, 3 and 8 of Cycles 1 and 5. Each cycle is 14 days in duration. | To evaluate the Maximum Plasma Concentration (Cmax) of NC410 |
| Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Approximately 1 year | To assess antitumor activity/efficacy by evaluating objective response rate (ORR), defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Overall Survival (OS) as Assessed by Time of Death | Approximately 1 year | To evaluate overall survival (OS), defined as the time from the first dose of NC410 to death due to any cause. |
| Area Under the Curve (AUC) of NC410 | Days 1, 2, 3 and 8 of Cycles 1 and 5. Each cycle is 14 days in duration. | To evaluate the Area Under the Curve (AUC) of NC410. |
| Half-life (t1/2) of NC410 | Days 1, 2, 3 and 8 of Cycles 1 and 5. Each cycle is 14 days in duration. | To evaluate the half-life (t1/2) of NC410 |
| Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | Approximately 1 year | To evaluate progression-free survival (PFS), defined as the time from the first dose of NC410 to the first occurrence of documented progressive disease or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), asa 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions . |
Countries
United States
Participant flow
Recruitment details
46 participants took part in the study at 5 investigative sites in the United States from 10Jun2020 to 06Jul2023.
Pre-assignment details
Phase 1a (Dose Escalation) consisted of 7 planned cohorts (NC410 IV doses 3mg to 200mg). Phase 1b (Safety Expansion) consisted of 3 cohorts (NC410 IV doses 30mg , 60mg and 100mg). Phase 1 enrolled 46 participants. NextCure decided to forgoe moving forward with NC10 as a monotherapy in Phase 2.
Participants by arm
| Arm | Count |
|---|---|
| NC410 3mg 3mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 3 |
| NC410 6mg 6mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 3 |
| NC410 15mg 15mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 4 |
| NC410 30mg 30mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 10 |
| NC410 60mg 60mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 10 |
| NC410 100mg 100mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 10 |
| NC410 200mg 200mg of NC410 for IV infusion administered in 14 day dosing cycles
NC410: NC410 is an experimental antibody drug that may make the immune response more active against cancer | 6 |
| Total | 46 |
Baseline characteristics
| Characteristic | NC410 3mg | Total | NC410 200mg | NC410 100mg | NC410 60mg | NC410 30mg | NC410 15mg | NC410 6mg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 7.64 | 61.0 years STANDARD_DEVIATION 11.77 | 66.0 years STANDARD_DEVIATION 7.48 | 59.3 years STANDARD_DEVIATION 9.46 | 66.3 years STANDARD_DEVIATION 14.69 | 58.2 years STANDARD_DEVIATION 14.44 | 59.0 years STANDARD_DEVIATION 2.45 | 61.3 years STANDARD_DEVIATION 13.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 42 Participants | 5 Participants | 9 Participants | 10 Participants | 10 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 11 Participants | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 30 Participants | 4 Participants | 7 Participants | 5 Participants | 5 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 3 Participants | 46 Participants | 6 Participants | 10 Participants | 10 Participants | 10 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 28 Participants | 5 Participants | 7 Participants | 3 Participants | 7 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 18 Participants | 1 Participants | 3 Participants | 7 Participants | 3 Participants | 2 Participants | 1 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 2 / 3 | 0 / 4 | 2 / 10 | 4 / 10 | 3 / 10 | 1 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 9 / 10 | 10 / 10 | 9 / 10 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 3 / 3 | 2 / 4 | 5 / 10 | 5 / 10 | 7 / 10 | 3 / 6 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0
Number of Participants With Treatment-emergent Adverse Events
Time frame: From enrollment through up to 90 days after end of treatment, an average of 1 year
Population: The Safety Analysis Set (SAS) will include all the subjects who receive any amount of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NC410 3mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 3 Participants |
| NC410 6mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 3 Participants |
| NC410 15mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 4 Participants |
| NC410 30mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 9 Participants |
| NC410 60mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 10 Participants |
| NC410 100mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 9 Participants |
| NC410 200mg | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0 | 6 Participants |
Secondary
Area Under the Curve (AUC) of NC410
To evaluate the Area Under the Curve (AUC) of NC410.
Time frame: Days 1, 2, 3 and 8 of Cycles 1 and 5. Each cycle is 14 days in duration.
Population: The PK analysis set (PAS) will include all the subjects whose blood samples are collected for PK analysis. AUC to Last Nonzero concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NC410 15mg | Area Under the Curve (AUC) of NC410 | Cycle 5 | 1056 h*ng/mL | — |
| NC410 30mg | Area Under the Curve (AUC) of NC410 | Cycle 5 | 47324 h*ng/mL | Standard Deviation 3674 |
| NC410 30mg | Area Under the Curve (AUC) of NC410 | Cycle 1 | 13528 h*ng/mL | Standard Deviation 15259 |
| NC410 60mg | Area Under the Curve (AUC) of NC410 | Cycle 1 | 64530 h*ng/mL | Standard Deviation 38613 |
| NC410 60mg | Area Under the Curve (AUC) of NC410 | Cycle 5 | 41448 h*ng/mL | — |
| NC410 100mg | Area Under the Curve (AUC) of NC410 | Cycle 1 | 107591 h*ng/mL | Standard Deviation 52432 |
| NC410 100mg | Area Under the Curve (AUC) of NC410 | Cycle 5 | 205493 h*ng/mL | — |
| NC410 200mg | Area Under the Curve (AUC) of NC410 | Cycle 5 | 260199 h*ng/mL | — |
| NC410 200mg | Area Under the Curve (AUC) of NC410 | Cycle 1 | 263894 h*ng/mL | Standard Deviation 121831 |
Secondary
Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
To assess antitumor activity/efficacy by evaluating disease control rate (DCR), defined as the proportion of participants in whom a documented complete response, partial response, or stable disease is observed as the best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Approximately 1 year
Population: The FAS includes all subjects enrolled in the study who received at least one full dose of NC410
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NC410 3mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| NC410 6mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 3 Participants |
| NC410 15mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| NC410 30mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| NC410 60mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| NC410 100mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| NC410 200mg | Disease Control Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
Secondary
Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors
To assess antitumor activity/efficacy by evaluating duration of response (DoR), defined as the time from the first documented complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Modified Response Evaluation Criteria in Solid Tumors to the first documented progressive disease or death due to any cause, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: CompleteResponse (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions .
Time frame: Approximately 1 year
Population: The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC410.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NC410 3mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
| NC410 6mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
| NC410 15mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
| NC410 30mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
| NC410 60mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
| NC410 100mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
| NC410 200mg | Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | NA months |
Secondary
Half-life (t1/2) of NC410
To evaluate the half-life (t1/2) of NC410
Time frame: Days 1, 2, 3 and 8 of Cycles 1 and 5. Each cycle is 14 days in duration.
Population: The PK analysis set (PAS) will include all the subjects whose blood samples are collected for PK analysis. Half-Life Lambda z (h).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NC410 30mg | Half-life (t1/2) of NC410 | Cycle 1 | 75.7 hours | Standard Deviation 74.7 |
| NC410 30mg | Half-life (t1/2) of NC410 | Cycle 5 | 138 hours | Standard Deviation 7.23 |
| NC410 60mg | Half-life (t1/2) of NC410 | Cycle 5 | 41.1 hours | — |
| NC410 60mg | Half-life (t1/2) of NC410 | Cycle 1 | 126 hours | Standard Deviation 52 |
| NC410 100mg | Half-life (t1/2) of NC410 | Cycle 1 | 173 hours | Standard Deviation 43.6 |
| NC410 100mg | Half-life (t1/2) of NC410 | Cycle 5 | 156 hours | — |
| NC410 200mg | Half-life (t1/2) of NC410 | Cycle 1 | 111 hours | Standard Deviation 53.8 |
| NC410 200mg | Half-life (t1/2) of NC410 | Cycle 5 | 194 hours | — |
Secondary
Maximum Plasma Concentration (Cmax) of NC410
To evaluate the Maximum Plasma Concentration (Cmax) of NC410
Time frame: Days 1, 2, 3 and 8 of Cycles 1 and 5. Each cycle is 14 days in duration.
Population: The PK analysis set (PAS) will include all the subjects whose blood samples are collected for PK analysis.~One subject within NC410 100mg Arm/Group has been excluded from the summary table due to the day 1 pre-infusion and post-infusion concentration values being incorrect
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NC410 15mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 5 | 443 ng/mL | — |
| NC410 15mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 1 | NA ng/mL | — |
| NC410 30mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 1 | 754 ng/mL | Standard Deviation 295 |
| NC410 30mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 5 | 1490 ng/mL | Standard Deviation 184 |
| NC410 60mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 1 | 2801 ng/mL | Standard Deviation 1102 |
| NC410 60mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 5 | 2200 ng/mL | — |
| NC410 100mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 1 | 5296 ng/mL | Standard Deviation 4405 |
| NC410 100mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 5 | 2220 ng/mL | — |
| NC410 200mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 5 | 2880 ng/mL | — |
| NC410 200mg | Maximum Plasma Concentration (Cmax) of NC410 | Cycle 1 | 11665 ng/mL | Standard Deviation 9821 |
Secondary
Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
To assess antitumor activity/efficacy by evaluating objective response rate (ORR), defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Approximately 1 year
Population: The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC410.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NC410 3mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| NC410 6mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| NC410 15mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| NC410 30mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| NC410 60mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| NC410 100mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| NC410 200mg | Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
Secondary
Overall Survival (OS) as Assessed by Time of Death
To evaluate overall survival (OS), defined as the time from the first dose of NC410 to death due to any cause.
Time frame: Approximately 1 year
Population: The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC410.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NC410 3mg | Overall Survival (OS) as Assessed by Time of Death | NA months |
| NC410 6mg | Overall Survival (OS) as Assessed by Time of Death | 5.3 months |
| NC410 15mg | Overall Survival (OS) as Assessed by Time of Death | NA months |
| NC410 30mg | Overall Survival (OS) as Assessed by Time of Death | NA months |
| NC410 60mg | Overall Survival (OS) as Assessed by Time of Death | 4.8 months |
| NC410 100mg | Overall Survival (OS) as Assessed by Time of Death | NA months |
| NC410 200mg | Overall Survival (OS) as Assessed by Time of Death | NA months |
Secondary
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors
To evaluate progression-free survival (PFS), defined as the time from the first dose of NC410 to the first occurrence of documented progressive disease or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), asa 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions .
Time frame: Approximately 1 year
Population: The FAS includes all subjects enrolled in the study who received at least one full dose of NC410
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NC410 3mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 1.7 Months |
| NC410 6mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 3.6 Months |
| NC410 15mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 1.3 Months |
| NC410 30mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 1.7 Months |
| NC410 60mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 1.4 Months |
| NC410 100mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 1.4 Months |
| NC410 200mg | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors | 1.8 Months |