This study is currently recruiting participants.
Many current cancer treatments, called immunotherapy, work by enhancing the body s own immune system's ability to attack tumors. Different immunotherapies work in different ways. Yet none of these treatments work equally well against all tumors. New approaches are needed.
To test a study drug (STAR0602) alone or in combination with chemotherapy in people with advanced solid tumors.
People aged 18 years and older with an advanced solid tumor, and their current treatment is no longer working.
Participants will be screened. They will have blood and urine tests and tests of their heart function. Their ability to perform daily tasks will be assessed. They will have imaging scans at screening; these will continue every 2 months during the study. Participants may need to have a biopsy, a small sample of tumor tissue removed, for screening; if they have already had a biopsy, that sample may be used.
Participants will receive the study drug through a tube attached to a needle placed in a vein. They will receive the drug 2 times during a 28-day cycle or 2 times during a 21 day cycle. Some participants may be required to stay in the hospital for 96 hours after receiving the drug.
Participants may have an additional tumor biopsy during their first treatment cycle.
Participants may continue to receive the study drug for up to 4 years. They will visit the clinic 2 months after their last treatment. Further follow-ups will occur by email or phone every 2 months for at least 12 months.
INCLUSION CRITERIA:
Each subject must also meet all the following criteria to be enrolled in this study:
General:
1. Age >= 18 years old.
2. Eastern Cooperative Oncology Group (ECOG) performance status of <= 1.
3. Ability to provide written informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the participant's disease. Participants must also be willing and able to comply with study procedures, including the acquisition of specified research specimens.
4. Life expectancy >=12 weeks.
5. Measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI. Cutaneous or subcutaneous lesions must be measurable by calipers. Lesions to be used as measurable disease for the purpose of response assessment must either: a) not reside in a field that has been subjected to prior radiotherapy; or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment.
Tumor Histology Types
6. For Phase 1, subjects must have one of the following solid tumors:
a. High mutational burden (TMB-H per local institutional testing); Tumor specimen is preferred (>= 10 mut/Mb), but if not available, liquid biopsy is allowed;
(If a patient's TMB is between 9-10 mut/Mb, the patient may be eligible for enrollment upon approval by the Sponsor.)
b. MSI-H/dMMR cancer (per local institutional testing); Tumor specimen is preferred, but if not available, liquid biopsy is allowed;
c. Virally associated tumors such as Merkel cell carcinoma, cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers, or EBV-related solid tumors. No viral testing required for Merkel cell carcinoma, cervical, or anal cancers. For oropharyngeal, penile, vaginal, and vulvar cancers, human papilloma virus (HPV) positivity documented per local institutional testing is required. For EBV-related solid tumors, EBV positivity documented per local institutional testing is required.
d. Solid tumors generally considered as immunogenic (e.g., melanoma and renal cell carcinoma) are eligible without prior testing for TMB, MSI or viral status after the Sponsor's approval;
7. For Phase 2, participants must have one of the following solid tumors:
a.High mutational burden (TMB-H >= 10 mut/Mb per local site testing). Tumor specimen is preferred, but if not available, liquid biopsy is allowed;
(If a patient's TMB is between 9-10 mut/Mb, the patient may be eligible for enrollment upon approval by the sponsor.)
b. MSI-H/dMMR cancer (per local site testing). Tumor specimen is preferred, but if not available, liquid biopsy is allowed;
c. CRC (both Ras wild-type and mutant) TMB-H, or MSI-H/dMMR, or both TMB-H and MSI-H/dMMR as defined above;
d. Virally associated tumors such as Merkel cell carcinoma, cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers, or EBV-related solid tumors. No viral testing required for Merkel cell carcinoma, cervical or anal cancers. For oropharyngeal, penile, vaginal, and vulvar cancers, HPV positivity documented per local institutional testing is required. For EBV-related solid tumors, EBV positivity documented per local institutional testing is required;
e. Metastatic triple-negative breast cancer (mTNBC);
f. Platinum-resistant epithelial ovarian cancer;
g. Metastatic castration-resistant prostate cancer (mCRPC);
h. Primary stage 4 or recurrent non-small cell lung cancer (NSCLC) - STAR0602 in combination with docetaxel (standard of care) as second-line therapy:
--Documented disease progression after, or intolerant to, the first-line systemic standard of care therapy (anti-PD1/anti-PDL1 based immunotherapy +/- chemotherapy, including maintenance therapy);
--Therapies targeting VEGF, CTLA-4, LAG3, or anti-PD1/anti-PD-L1-based bispecific included in the first-line therapy are allowed. Sponsor's approval is required for participants who have received other investigational agents used in the first-line therapy;
--Participants with known targetable/actionable mutations or genomic alterations (e.g., EGFR, ALK, ROS1, BRAF, NRG1, KRAS, MET, RET, HER2, HGF, NTRK1,2,3) may be eligible provided they have received at least one target therapy for the known genomic alteration.
--Non-bulky liver metastases (< 5 cm) allowed;
i. Solid tumors generally considered as immunogenic (e.g., melanoma and renal cell carcinoma) are eligible without prior testing for TMB, MSI or viral status after the Sponsor's approval;
j. Metastatic CRC (mCRC) with proficient DNA mismatch repair/microsatellite stable (mCRC with pMMR/MSS without TMB requirement) - STAR0602 in combination with irinotecan (standard of care) as second-line therapy:
--Documented disease progression after, or intolerant to, the first-line systemic therapy of 5-FU + oxaliplatin-based standard of care regimens or within 6 months after the start of adjuvant therapy with these regimens;
--The following agents included in first-line therapy are allowed: bevacizumab, cetuximab, panitumumab and targeted agents such as BRAF V600E inhibitors, anti-PD1/anti-PD-L1-based bispecifics. Sponsor's approval is needed for participants who have received other investigational agents as first-line therapy;
--UGT1A1 gene testing prior to enrollment to determine the homozygosity for the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or compound heterozygosity for the UGT1A1*28 and *6 alleles (*6/*28). These genotypes increase the risk of severe neutropenia during treatment with irinotecan and require a mandatory reduction of irinotecan starting dose by at least one dose level per irinotecan USPI20, PM21, or
SmPC22; Homozygosity of 28/28 and 6/6 will be excluded. Enrollment of participants with heterozygosity of these alleles needs the sponsor's approval. In geographic regions where standard UGT1A1 testing is not accessible, research use only (RUO) lab testing is allowed.
--Not eligible if treated with irinotecan-based first-line therapy;
--Non-bulky liver metastases (defined as < 5 cm) allowed;
Other histologies may also be included in Phase 2 as additional data emerge to support their inclusion.
Tumor Specimen:
8. Participants must allow for acquisition of existing formalin-fixed paraffin-embedded archival tumor sample, either a block or unstained slides that had been procured within 3 months prior to enrollment, if available. The subject also must not have received intervening therapy between archival specimen collection and the first dose of STAR0602.
9. If a study site cannot retrieve such existing archival tumor sample within 2 weeks after the initial attempt, or archival tumor is not available, the following participants must consent to fresh baseline tumor biopsy during Screening:
-Dose Escalation (Phase 1) participants: only after a dose escalation cohort is identified with clear evidence of STAR0602 biological effect (e.g., expansion of target T cell subsets, anti-tumor effect, or other relevant biomarker assessments), i.e., participants still enrolling in this dose escalation cohort and at the higher dose levels thereafter;
-Backfill participants (in Dose Escalation): the additional participants enrolled in Dose Escalation at a dose level deemed below or at the MTD;
-Dose Expansion Cohort (Phase 2) participants.
Above participants must also consent to a second tumor biopsy 21 days (+/- 3 days) after the first dose administration of STAR0602.
Note: Per the investigator's discretion, if biopsy is strenuous to obtain, e.g., no easily accessible lesions are available or the subject condition is not amenable for biopsy, then the subject will be eligible for enrollment without biopsy at screening and for continuation of treatment without biopsy on treatment.
Laboratory Features:
10. Acceptable laboratory parameters as follows:
-Albumin >= 3.0 g/dL;
-Platelet count >= 75 x 103/micro L;
-Hemoglobin >= 8.5 g/dL;
-Absolute neutrophil count (ANC) >= 1.5 x 103/micro L; (participants with duffy-null phenotype who have baseline ANC lower than this criterion may be enrolled upon the approval by the Sponsor);
-ALT/AST <= 3.0 x upper limit of normal (ULN); <= 5.0 X ULN with hepatic metastases; Phase 2 Cohort 8, <= 1.5 ULN)
-Total bilirubin <= 1.5 x ULN (Phase 2 Cohort 8 < ULN), except participants with Gilbert's syndrome, who may be enrolled if the conjugated bilirubin is within normal limits or approved by the Sponsor.
-Calculated creatinine clearance >= 50 mL/min (based on Cockcroft-Gault formula or on a 24-hour urine collection). For over- or under- weight participants, ideal body weight should be used for calculating the creatinine clearance.
Reproductive Features:
11. Female participants of childbearing potential (not surgically sterilized and between menarche and 1-year post-menopause) must have a negative serum (screening) or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female participants of childbearing potential must be willing to use a condom plus 1 of the highly effective methods of contraception throughout the study, from the time of consent through 60 days after the last dose of STAR0602. Examples of effective contraception are birth control pills, birth control patch (e.g., Ortho Evra), NuvaRing, intrauterine device, female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner, documented sterile sexual partner or documented evidence of surgical sterilization (e.g., tubal ligation or hysterectomy) at least 6 months prior to Screening. Abstinence is acceptable if this is the established and the preferred contraception method for the subject. It is not necessary to use any other method of contraception when complete abstinence is elected.
12. Male participants with partners of childbearing potential must use barrier contraception from the time of consent through 60 days after last dose of STAR0602 and must not donate sperm during this period. In addition, male participants should also have their partners use contraception (as documented for female participants) for the same period of time.
CNS Metastases:
13. Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for >= 14 days, and meet the following at the time of enrollment:
-No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids > 10 mg prednisone/day or equivalent);
-No concurrent leptomeningeal disease or cord compression.
Previous Checkpoint Inhibitor Therapy:
14. Participants who have previously received a CPI (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have CPI immune-related toxicity resolved to either Grade <= 1 or baseline (prior to the CPI) to be eligible for enrollment.
-Participants who experienced previous CPI-related endocrine abnormalities are eligible for the study regardless of CTCAE grade if well controlled on replacement therapy.
-Participants who have had previous CPI-related Grade 3 to 4 pneumonitis, peri/myocarditis, colitis and bowel perforation, myositis, encephalitis, or peripheral neuropathy need to be discussed with and approved by the Sponsor and Medical Monitor.
EXCLUSION CRITERIA:
Participants who meet any of the following criteria will be excluded from the study:
1. Participants with a history of known autoimmune disease with exceptions of:
-Vitiligo;
-Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiring systemic treatment;
-History of Graves' disease, now euthyroid for > 4 weeks;
-Hypothyroidism managed by thyroid replacement;
-Alopecia;
-Arthritis managed without systemic therapy beyond oral nonsteroidal anti-inflammatory drugs.
-Adrenal insufficiency- well controlled on replacement therapy.
2. Major surgery or traumatic injury within 8 weeks before first dose of study drug.
3. Unhealed wounds from surgery or injury.
4. Treatment with >10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within 7 days prior to the initiation of study drug. Exceptions may be made for patients who have had allergic reaction to iodinated contrast media. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed.
5. Prior therapy within the following timeframe before the planned infusion of STAR0602 as follows:
-Cytotoxic chemotherapy, small molecule inhibitors, radiation, interventional radiology procedure, or similar investigational therapies within <= 2 weeks or participants who have not recovered (i.e., <= Grade 1 or to baseline) from AEs due to a previously administered agent;
-Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar investigational therapies within 6 weeks prior to the initiation of study drug or participants who have not recovered (i.e., <= Grade 1 or to baseline) from AEs due to agents administered more than 6 weeks earlier.
Note: Participants with <=Grade 2 neuropathy or <= Grade 2 alopecia are an exception to this criterion and may qualify for the study.
Note: Concurrent use of hormones either to maintain castrate levels of testosterone in participants with castration-sensitive prostate cancer or for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates are permitted for supportive care of bone metastases (e.g., breast or prostate cancer).
6. Clinically significant cardiovascular/vascular disease including:
-Myocardial infarction or unstable angina < 6 months prior to the initiation of study drug;
-Clinically significant cardiac arrhythmia (e.g., with potential for hemodynamic instability) not controlled or unresponsive to treatment;
-Uncontrolled hypertension: systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg; Participants with systolic blood pressure > 140 mmHg but < 180 mmHg and/or diastolic blood pressure > 90 mmHg but < 100 mmHg may be enrolled upon reviewing co-morbidities/risks and after the sponsor approval. These participants need to be closely monitored with their blood pressure assessed and managed at each visit on treatment;
-Pulmonary embolism, stroke, or transient ischemic attack < 6 months prior to initiation of STAR0602;
-QTcF (Fridericia correction) prolongation > 480 msec;
-Congestive heart failure (New York Heart Association Class III-IV);
-Pericarditis/clinically significant pericardial effusion;
-Myocarditis;
-Vasculitis that has not resolved within 6 months prior to study drug.
7. Clinically significant gastrointestinal disorders including:
-Gastrointestinal perforation < 6 months prior to study drug administration. Participants must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior perforation;
-Gastrointestinal bleeding < 2 months prior to study drug administration. Participants must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior bleeding;
-Pancreatitis <6 months prior to the initiation of study drug. Participants must have a CT scan negative for evidence of remaining disease or normal pancreatic enzyme levels for > 4 weeks prior to the initiation of study drug;
-Diverticulitis flare < 2 months prior to study drug administration. Participants must have a CT scan negative for evidence of remaining disease prior to the initiation of study drug;
-History of Crohn's disease or ulcerative colitis.
8. Inflammatory process that has not resolved for >= 4 weeks from the date of first study dose. Participants with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of duration.
9. Clinically significant pulmonary compromise (e.g., requirement for supplemental oxygen on a continuous basis).
10. Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Systemic antiviral, antifungal, or antibacterial therapy must be completed > 1 week prior to the initiation of study drug. Antimicrobial prophylaxis (e.g., for pneumocystis carinii infection) may continue the antimicrobial for that purpose.
11. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
12. Participants who are known to be human immunodeficiency virus (HIV) positive or hepatitis B or C positive and have uncontrolled disease. Participants treated for hepatitis C must have viral titers below the limit of quantification to be eligible. Participants with hepatitis B having undetectable or <= 500 IU/mL hepatitis B viral DNA are eligible for STAR0602. Participants treated for HIV must have CD4+ T cell (CD4+) counts >= 350 cells/micro L and HIV viral load less than 400 copies/mL to be eligible.
13. Second primary invasive malignancy not in remission for >= 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score <= 7), resected melanoma in situ, or any malignancy considered to be indolent and never required systemic therapy, with the exception of indolent lymphomas.
14. Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the subject to receive or tolerate the planned treatment.
15. Known hypersensitivity to STAR0602 or any excipient (histidine or polysorbate-80) contained in the drug or diluent formulation.
16. Any medical (e.g., requirement of an indwelling catheter such as PleurX or Tenckhoff catheter) or non-medical issue that would contraindicate the participants's participation in the study or confound the results of the study.
17. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation).
18. Hepatic metastases unless a) adequately treated, either locally (e.g., by surgery, radiofrequency ablation, or chemoembolization) or systemically or both, and stable for 2-3 months, b) <= 3 lesions and no lesion >= 3 cm in greatest dimension for monotherapy Cohorts 1-7 and 9, or c) Phase 2 Cohort 8 (primary stage 4 or recurrent NSCLC) or Cohort 10 (mCRC with pMMR/MSS without TMB requirement).
19. Bulky disease defined as any lesion >= 5 cm in greatest dimension unless approved by the Sponsor.