Inclusion Criteria:

• Adult age 18 years or older and willing and able to provide written informed consent.
• Histologically or cytologically confirmed advanced metastatic or unresectable CRC that is relapsed, refractory, or progressive following at least 2 prior systemic regimens in the metastatic setting and for which no further standard or curative therapy exists or is considered appropriate by the Investigator. In addition, subjects with CRC tumors that are microsatellite instability-high (MSI-H) should have been previously treated with either nivolumab or pembrolizumab.
• Measurable disease is defined as at least 1 tumor lesion ≥10 mm in the longest diameter or a lymph node ≥15 mm in short axis measurement assessed by computerized tomography (CT) scan per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). For dose levels at which single subject cohorts are planned, measurable disease is not required.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Minimum life expectancy of at least 12 weeks
• Availability of fresh or archived tumor tissue representative of the qualifying malignancy and suitable for immunohistochemistry (IHC) testing. The tumor tissue may consist of an optional fresh biopsy, or a formalin fixed paraffin embedded (FFPE) block with enough tissue left to cut at least 10 slides with 4 μm thickness, or at least 10 FFPE unstained slides with 4 μm thickness cut within 2 weeks of shipment. For dose levels at which single-subject cohorts are planned, provision of tumor tissue, FFPE block, or FFPE unstained slides is not required.
• Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved brain imaging for at least 2 weeks after completion of definitive treatment, and within 2 weeks prior to first dose of study drug, off corticosteroids. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy.
• Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia and peripheral neuropathy) prior to initiation of study drug administration.
• Satisfactory laboratory parameters:
  • Absolute neutrophil count (ANC) ≥500/μL;
  • Platelet count >140,000/μL;
  • Hemoglobin ≥.0 g/dL;
  • Serum total bilirubin ≤.5× ULN or ≤× ULN for subjects with Gilbert’s disease;
  • Serum ALT and AST ≤× ULN (≤× ULN if evidence of hepatic involvement bymalignant disease);
  • Serum creatinine ≤.5× ULN or estimated filtration rate (eGFR) ≥0 mL/min/1.73m2(using MDRD [Modification of Diet in Renal Disease] formula);
  • Serum albumin ≥ g/dL;
  • Amylase and lipase ≤.5× ULN (≤× ULN if amylase or lipase is isolated with neitherclinical nor radiographic signs of pancreatitis).
• Last dose of any prior therapy administered before the first dose of study drug:
  • Chemotherapy, small molecule inhibitors, radiation, and/or other investigationalanticancer agents (excluding investigational monoclonal antibodies): 2 weeks before thefirst dose of study drug;
  • Prior therapy with any agents targeting immune coinhibitory receptors (e.g., anti-PD-1,anti-PD-L1, anti-PD-L2, anti-CTLA-4), or costimulatory receptor activators,monoclonal antibodies, antibody drug conjugates, radioimmunoconjugates, or T-cell orother cell-based therapies: 4 weeks (2 weeks permissible before the first dose of studydrug, if unequivocal PD is documented).
• If female, subject must be either postmenopausal, OR permanently surgically sterile OR forwomen of childbearing potential (WOCBP) practicing at least one protocol-specifiedmethod of birth control (Section 7.3.3), starting at Study Day 1 through at least 6 monthsafter the last dose of study drug.
• If the male subject is sexually active with female partner(s) of childbearing potential, he must agree to practice the protocol specified contraception (Section 7.3.3) from Study Day 1 through at least 6 months after the last dose the study drug.
• Females of childbearing potential must have a negative serum pregnancy test result at Screening and a predose negative urine pregnancy test on Cycle 1 Day 1 (C1D1). Females of nonchildbearing potential (either postmenopausal or permanently surgically sterile as defined in Section 7.3.3) at Screening do not require pregnancy testing.

Exclusion Criteria:

• Any significant medical condition, including any suggested by screening laboratoryfindings that, in the opinion of the Investigator or Sponsor, may place the subject at unduerisk from the study.
• Documented history of stroke or transient ischemic attack, unstable angina, myocardialinfarction, congestive heart failure consistent with New York Heart Association (NYHA)Class III–IV (Appendix 14.7), uncorrected hypocalcemia (≤.2 mg/dL), or other clinicallysignificant cardiac disease within 6 months prior to the first dose of study drug. Subjects with history of congestive heart failure must have cardiac echocardiogram (ECHO) indicating left ventricular ejection fraction (LVEF) ≥45% within 28 days prior to first dose of study drug.
• Has electrocardiogram (ECG) abnormalities that make QT interval corrected using Fridericia’s formula (QTcF) evaluation difficult (e.g., severe morphologic abnormalities).
• Has a history of cardiac conduction abnormalities including:
  • QTcF >470 msec;
  • ECG with second degree type 2 or third degree atrioventricular block, and left bundle branch block;
  • Persistent bradycardia as defined by sinus rate <45 beats per minute or persistent tachycardia >120 beats per minute.
• Recent or ongoing serious infection, including:
  • Any active Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted;
  • Known seropositivity for or active infection by human immunodeficiency virus (HIV);
  • Active hepatitis B (e.g., surface antigen positive or core antibody positive with viremia), or active hepatitis C (e.g., antibody positive with viremia) or on hepatitis-related antiviral therapy (excluding prevention) within 6 months of first dose of study drug.
• Female subject who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 6 months after the last dose of study drug.
• Male subject who is considering fathering a child or donating sperm during the study or for approximately 6 months after the last dose of study drug.
• Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug.
• Subject has a history of active malignancies other than CRC or gastric cancer within the 2 years prior to study entry, with the exception of in situ cancer which was curatively treated.
• Prior exposure to a PBD- or indolinobenzodiazepine-based drug, or known hypersensitivity or contraindication to SC-006 or excipient contained in the drug formulation.

Additional Exclusion Criteria for the SC-006 and ABBV-181 Combination Treatment Regimen:

• History of inflammatory bowel disease.
• Peripheral neuropathy Grade 2 with pain, or Grade 3 or higher.
• History of pneumonitis.
• Creatinine clearance (CrCl) <40 mL/minute (using MDRD formula or 24-hour urine creatinine clearance).
• Subjects who have been previously treated with an anti PD-1/PD-L1 targeting agent must not have had during the course of their therapy:
  • Any immune mediated toxicity of Grade 3 or worse severity;
  • Treatment for immune-related AE(s) with systemic corticosteroids;
  • Any hypersensitivity to PD-1/PD-L1 targeting agents.
• Subject is judged by the Investigator to have evidence of ongoing hemolysis on hemolysis panel (lactate dehydrogenase [LDH], total, direct and unconjugated serum bilirubin, peripheral blood smear, D-dimers and serum haptoglobin).
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection);
  • Systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Active autoimmune disease, with exceptions of psoriasis not requiring systemic treatment, vitiligo, type 1 diabetes mellitus, and hypothyroidism.
• History of primary immunodeficiency, allogeneic bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
• Subject with Hemoglobin <9.0 g/dL.