Lay Description

This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of Pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors


  • Cancers and Other Neoplasms
  • Immune System
  • Metastases
IRB Number
NCT Number registration not required
Open to Enrollment


Eligible Ages
18 and above
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

1) The participant (or legally acceptable representative if applicable) provides written

informed consent for the trial.

2) Be ≥ 18 years of age on day of signing informed consent.

3) Participant with histologically or cytologically confirmed diagnosis of the following

advanced unresectable and/or metastatic solid tumors:

a. Phase 1b: Participants with solid tumors that are known to be associated with

MSS/MSI-low in the majority including: CRC, Gastric including GE junction,

Esophageal, Ovarian, and H&N cancer (regardless of prior treatment with ICIs).

Note: Participants must have had disease progression after at least one line of

systemic standard of care therapy prior to enrollment. Participants who discontinue

standard treatment due to intolerance or refuse standard treatment will also be

eligible to enroll.

b. Phase 2 ICI Refractory (Cohort 1):

i. Participants with solid tumors including CRC, Gastric including GE

junction, Esophageal, Endometrial, and H&N cancer.

ii. Participants must have progressed on treatment with an anti-PD1/L1

monoclonal antibody (mAb) administered either as monotherapy, or in

combination with other checkpoint inhibitors or other therapies. PD-1

treatment progression is defined by meeting all of the following criteria:

1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.

2. Has demonstrated disease progression after PD-1/L1 as defined by

RECIST v1.1. The initial evidence of progressive disease is to be

confirmed by a second assessment no less than four weeks from the

date of the first documented progressive disease, in the absence of

rapid clinical progression.

3. Progressive disease has been documented within 12 weeks from the

last dose of anti-PD-1/L1 mAb.

a. Progressive disease is determined according to iRECIST.

b. This determination is made by the investigator. Once

progressive disease is confirmed, the initial date of

progressive disease documentation will be considered the

date of disease progression.

Phase 2 ICI naïve (Cohorts 2a-2c):

i. Tumors known to be associated with MSS/MSI-low status such as CRC,

Gastric including GE junction, and Ovarian where participants have not

been previously treated with ICIs.

Note: Participants must have had disease progression after at least one line

of systemic standard of care therapy prior to enrollment. Participants who

discontinue standard treatment due to intolerance or refuse standard

treatment will also be eligible to enroll.

Note: Confirmation of MSS/MSI status should be assessed prior to study

entry (either by historical result or during screening).

4) A male participant must agree to use contraception and refrain from sperm donation or

expecting to father a child, from Screening through the treatment period and for at least

120 days after the last dose of study treatment.

5) A female participant is eligible to participate if she is not pregnant, not breastfeeding, and

at least one of the following conditions applies:

a. Not a woman of childbearing potential (WOCBP)

b. A WOCBP who agrees to follow contraceptive guidance outlined in Section 6.2

from Screening through the treatment period and for at least 120 days after the last

dose of study treatment.

6) Have measurable disease per RECIST 1.1 as assessed by the local site

investigator/radiology. Lesions situated in a previously irradiated area are considered

measurable if progression has been demonstrated in such lesions.

7) Able to provide tumor tissue sample at Screening, archival (≤ 5 years old) or newly

obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalinfixed,

paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained

biopsies are preferred to archived tissue.

8) Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

9) Life expectancy greater than or equal to 12 weeks as judged by the Investigator.

10) Have adequate organ function as defined in the following table (Table 1). Specimens must

be collected within 10 days prior to the start of study treatment.

11) Participants who are HBsAg positive are eligible if they have received HBV antiviral

therapy for at least 4 weeks and have undetectable HBV viral load prior to screening.

Note: Participants should remain on anti-viral therapy throughout study intervention

and follow local guidelines for HBV anti-viral therapy post completion of study


Hepatitis B screening tests are not required unless:

a. Known history of HBV infection

b. As mandated by local health authority

12) Participants with history of HCV infection are eligible if HCV viral load is undetectable at


Note: Participants must have completed curative anti-viral therapy at least 4 weeks

prior to screening.

Hepatitis C screening tests are not required unless:

c. Known history of HCV infection

d. As mandated by local health authority

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

Pregnancy Exclusion

1) A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If

the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will

be required.

Prior/Concomitant Therapy

2) Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an

agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40,

CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE.

3) Has received prior systemic anti-cancer therapy including investigational agents within

4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs)

prior to treatment.

Note: Participants must have recovered from all AEs due to previous therapies to

≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.

Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone

replacement may be eligible.

Note: If the participant had major surgery, the participant must have recovered

adequately from the procedure and/or any complications from the surgery prior to

starting study intervention.

4) Has received prior radiotherapy within 2 weeks of start of study treatment or has had a

history of radiation pneumonitis.

Note: Participants must have recovered from all radiation-related toxicities and do not

require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2

weeks of radiotherapy) to non-CNS disease.

5) Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.

6) Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study


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.

7) Receipt of COVID-19 vaccine within ≤ 14 days prior to first administration of study


Note: For 2-dose COVID-19 vaccines or COVID-19 booster, participants must wait at

least 14-days after administration prior to beginning study treatment.

8) Is currently participating in or has participated in a study of an investigational agent or has

used an investigational device within 4 weeks prior to the first dose of study treatment.

Note: Participants who have entered the follow-up phase of an investigational study

may participate as long as it has been 4 weeks after the last dose of the previous

investigational agent.

9) Has had an allogeneic tissue/stem cell/solid organ transplant.

Diagnostic assessments

10) Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in

dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days prior to the first dose of study drug.

11) Has a known additional malignancy that is progressing or has required active treatment

within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of

the skin, or carcinoma in situ, excluding carcinoma in situ of bladder, that have

undergone potentially curative therapy are not excluded.

12) Has known active CNS metastases and/or carcinomatous meningitis. Participants with

previously treated brain metastases may participate provided they are radiologically stable,

i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the

repeat imaging should be performed during study screening), clinically stable and without

requirement of steroid treatment for at least 14 days prior to first dose of study treatment.

13) Has severe hypersensitivity (≥ Grade 3), known allergy or reaction to Pembrolizumab,

NC410, and/or any of their excipients.

14) Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e.,

with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).

Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement

therapy for adrenal or pituitary insufficiency) is not considered a form of systemic

treatment and is allowed.

15) Has a history of (non-infectious) pneumonitis / interstitial lung disease that required

steroids or has current pneumonitis / interstitial lung disease.

16) Has an active infection requiring systemic therapy.

17) Has a known history of HIV infection. No HIV testing is required unless mandated by local

health authority.

18) Has a history or current evidence of any condition, therapy, or laboratory abnormality, or

other circumstance that might confound the results of the study or interfere with the

participant's participation for the full duration of the study, such that it is not in the best

interest of the participant to participate, in the opinion of the treating investigator.

19) Has a known psychiatric or substance abuse disorder that would interfere with the

participant’s ability to cooperate with the requirements of the study.

Study Design

Arm Groups

Study Contact

Frances Crawford
(210) 450-5037

Sonia Creighton
(210) 450-1366

Myrna Montenegro
(210) 450-5954

Courtney Nichols
(210) 450-1794

Kathleen Rodriguez
(210) 450-1365

Benjamin Schleif
(210) 450-1366

Morgan Seekatz
(210) 450-1133

Principal Investigator
Daruka Mahadevan