1002-CL-0101: A Phase 1 Study of ASP1002 in participants with Metastatic or Locally Advanced Solid Tumors
Study Sponsor: Astellas Pharma Global Development, Inc.
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: Phase I
Purpose of study: This is a first-in-human study that is looking to study the safety, and tolerability to determine the maximum tolerated dose of study drug ASP1002. The study is open to multiple tumor types – NSCLC, US, CRC, prostate adenocarcinoma, ovarian, and triple negative breast cancer. It is made up of two parts – Part 1: Dose escalation, where the study will determine the highest dose tolerable, and Part 2: dose expansion, where the determined dose will be tested in the tumor types that had the best response to the study drug.
Inclusion Criteria
– Be 18 years or older at study start.
– Must have locally advanced or metastatic solid tumor as determined by pathology records or biopsy.
For dose escalation, patient must have one of the following tumor types: non small-cell lung cancer, urothelial carcinoma, colorectal cancer, prostate adenocarcinoma, epithelial ovarian cancer, or triple negative breast cancer.
For dose expansion, patient must have: NSCLC, UC, CRC, or any tumor type which had confirmed response observed during the dose escalation part.
– Has progressed on, is intolerant to, refused standard therapy, or there is no standard therapy that would provide clinical benefit. (No limit on prior number of lines of therapy)
– Patient has accessible archival tissue that is less than 6 months old from primary or metastatic site. Patients without available tissue will need to undergo biopsy, or if biopsy deemed unsafe, case may be discussed with the medical monitor. Additionally, will undergo an on-treatment biopsy.
– Must have at least 1 measurable lesion per RECIST 1.1
– Must have ECOG of 0 – 1.
– Must have completed previous radiotherapy at least 2 weeks prior to study start.
– Must have predicted life expectancy of at least 12 weeks per treating physician.
– Must have adequate organ function as determined by local lab tests, and lab values must be collected within 7 days prior to first dose.
– Female participant is not pregnant.
– Participants must agree to not breastfeed starting at screening, throughout the study, and for 90 days post last dose. Additionally, participants must agree to use highly effective forms of contraception and must not donate sperm from screening, while on study, and for 90 days post last dose.
– Must not participate in another interventional study while receiving ASP1002.
Additional criteria may apply and will be discussed with the study team and physician.
Exclusion Criteria:
– Weighs less than 40kg.
– Has grade 2 or higher toxicity per CTCAE that is due to prior therapies.
– Symptomatic central nervous system metastasis or uncontrolled CNS disease. (Patient with previously treated CNS mets may be eligible if they are clinically and radiologically stable for at least 4 weeks prior to study start, and are not currently on systemic steroids of 10mg prednisone or more per day)
– Patient has active autoimmune disease. Patients with type 1 diabetes, endocrinopathies, stable replacement therapy, or skin disorders such as alopecia, vitiligo, or psoriasis are allowed.
– Has myocardial infarct, or unstable angina within 6 months, or has symptomatic congestive heart failure or other clinically significant cardiac condition.
– Has QTcF of more than 470ms within 7 days of study start.
– LVEF< 45% per screening echocardiogram.
– Has known HIV infection. Patient is allowed if CD4+ T cell counts are equal to or greater than 350 cells/μL and patient has no history of AIDS defining opportunistic infections within the last 6 months.
– Positive serology testing.
– History of drug-induced pneumonitis, ILD, current pneumonitis, or prior history requiring high-dose glucocorticoids.
– Uncontrolled illness such as active infections, substance abuse or psychiatric illness, or social situations that would impact the patient’s ability to comply with study requirements.
– Prior bone marrow or solid organ transplant.
– Has had major surgery, and has not recovered, within 28 days prior to study start.
– Positive COVID-19 test within 10 days prior to study start.
– Has received any other investigational therapy, antineoplastic therapy, or immunotherapy within last 21 days.
– Requires or has received systemic steroid therapy or other immunosuppressive therapy within 14 days prior to first dose of study drug.
– Patient has discontinued prior immunomodulatory therapy due to grade 3 or higher that was immune-related and deemed life-threatening by the treating physician.
– Has other active malignancy requiring therapy.
– Has received prior anti-CD137 therapy.
– Received a live vaccine within last 28 days prior to study start.
Additional criteria may apply and will be discussed with the physician and study team.
Study Contact:
Lisa Wahowske
(651) 254-1517
lisa.wahowske@parknicollet.com
DB1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors
Study sponsor: Dualitybio Inc.
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: I
Purpose of study: This is a first-in-human study that is looking to test the safety and effectiveness of study drug DB-1311 in solid tumors. The study drug is an antibody-drug combination composed of an anti-B7-H3 antibody and P1021 (a topoisomerase I Inhibitor). It is thought that by interfering with the B7-H3 protein, this may inhibit the growth of cancer cells. P1021 works to promote cancer cell death by interrupting DNA replication. The thought is that combination of these will help target and help the body to destroy the tumor cells.
Inclusion Criteria:
– Must be 18 years or older.
– Confirmed advanced / metastatic solid tumor that progressed / relapsed on standard therapy.
– At least one measurable lesion per RECIST 1.1.
– Has life expectancy of at least 3 months.
– ECOG of 0 – 1.
– LVEF of at least 50%.
– Adequate organ function as determined by lab tests.
– Willing to provide existing tumor tissue samples or undergo fresh tumor biopsy for measurement of biomarkers.
– Male, and female subjects of childbearing potential must agree to highly effect methods of contraception.
– Male subjects must not freeze or donate sperm for at least 4 months after last dose of study drug. Female subjects must not donate, or retrieve ova from time of screening through at least 7 months after last dose of study drug.
Several other cohort specific criteria may apply for Phase 2a of the study depending on disease type.
Part 2a:
SCLC (Cohort 1) –
-Prior treatment with at least 1 platinum therapy for 2 cycles.
NSCLC (Cohort 2) –
-Has received treatment with platinum-based chemo, or anti-PD-1/PD-L1 therapy in advanced/metastatic setting. If patient has genomic mutations other than EGFR mutation, patient must also have been treated with at least 1 genotype-directed therapy.
ESCC (Cohort 3) –
-Received at least 1 prior therapy for unresectable disease.
CRPC (Cohort 4) –
-Progressive metastatic CRPC as defined by PCWG3 criteria.
-Has received prior docetaxel.
-Has received prior novel hormone therapy.
Melanoma (Cohort 5) –
-Confirmed Stage 3 or metastatic melanoma
-Must previously have been treated with PD-1 or PD-L1 inhibitor.
-If pt. has BRAF mutant melanoma, must have had prior treatment that included a BRAF gene or MEK inhibitor.
HCC (Cohort 6) –
-Confirmed HCC and has received 1 or 2 prior systemic regimens for metastatic disease.
-Has experienced progression during or after treatment with anti-PD-1/L1 agent given as monotherapy or combination.
Cervical Cancer (Cohort 7) –
-Recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous histology, and has experienced disease progression during or after treatment with standard of care platinum or doublet therapy.
Other Solid Tumors (Cohort 8) –
-Must have progressed after at least 1 prior standard therapy.
Additional criteria may apply and will be discussed with study team and physician.
Exclusion Criteria:
– Prior treatment with B7-H3 targeted therapy.
– Prior treatment with antibody drug conjugate with topoisomerase inhibitor (such as trastuzumab deruxtecan).
– Has medical history of symptomatic congestive heart failure NYHA class II-IV or serious cardiac arrhythmia requiring treatment.
– Medical history of myocardial infarct or unstable angina within 6 months prior to enrollment.
– Average QTcF > 470 based on ECG results.
– Unable or unwilling to discontinue concomitant medications that are known to prolong QT interval.
– Medical history of interstitial lung disease or has current interstitial lung disease.
– History of underlying pulmonary disorder (pulmonary emboli, severe asthma, COPD, restrictive lung disease, or other significant pulmonary disease that requires supplemental oxygen for treatment).
– Autoimmune, connective tissue, inflammatory disorder where there is suspicion of pulmonary involvement at screening.
– Uncontrolled infection requiring antibiotics, antivirals, or antifungals.
– Known HIV infection.
– Active hepatitis infection. Patients with history of, may be eligible after completing curative treatment, and have viral load below quantification limit.
– Lactating mother, or pregnant within 7 days prior to enrolling into the study.
– Spinal cord compressions or active nervous system metastases that requires corticosteroids. Patients with asymptomatic, radiologically and neurologically stable disease for at least 4 weeks are eligible.
– Has unresolved toxicity from previous anticancer therapy. May be eligible after discussion between treating physician and sponsor.
– Has multiple primary malignancies within 3 years.
– Has substance abuse issues or other medical conditions that, in physician opinion, would interfere with patient’s ability to participate in the study.
Additional exclusion criteria may apply and will be discussed with study team and physician.
Study Contact:
Lisa Wahowske, RN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
HERTHENA-PanTumor01 (U31402-277): A Phase 2, Multicenter, Multicohort, Open-Label, Proof of Concept Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Subjects with Locally Advanced or Metastatic Solid Tumors
Study sponsor: Daiichi Sankyo
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: II
Purpose of study: The purpose of the study is to determine safety and effectiveness of the study drug Partitumab Deruxtecan (also known as HER3-DXd or U3-1402). The study drug is known as an Antibody Drug Conjugate (or ADC). An antibody is a protein that is produced by the immune system to identify and get rid of foreign objects like bacteria. ADCs are composed of an antibody attached to an anticancer drug. ADCs are made to attach to tumor cells. Once attached to the cell, the ADC is taken inside the tumor cell and the anticancer drug is released inside to kill the cancer cell.
Inclusion Criteria:
– Must be at least 18 years or older.
– Must have locally advanced unresectable or metastatic disease.
– At least 1 measurable lesion per RECIST 1.1 via CT or MRI. Prostate cancer subjects with bone only lesion may be eligible.
– Able to provide pre-treatment tissue as the following: a. Tissue collected from biopsy that was performed since progressing while on, or after treatment with the most recent systemic cancer therapy prior to signing consent, OR b. patient is amenable to a pre-treatment biopsy after signing informed consent for the study. (Pretreatment tissue requirement may potentially be waived if discussed with, and approved by the medical monitor)
– ECOG of 0 – 1.
– Has adequate organ function as determined by local lab tests.
– Female patients of childbearing potential, and male patients with partners of childbearing potential must agree to use highly effective forms of birth control during the treatment period and for at least 4 months after the last dose of study drug. Additionally, female patients may not donate or retrieve ova from time of screening through at least 7 months after last dose of study drug, and male patients may not donate or freeze sperm from time of screening through 4 months after the last dose.
– Must be willing to comply with scheduled visits, drug administration plan, lab tests, and other study procedures, and must adhere to study restrictions.
Cohort specific criteria below:
– Cutaneous (acral and non-acral) melanoma:
a. Histologically or cytologically confirmed cutaneous melanoma.
b. disease progression while having received treatment with at least 1 prior line of anti-PD-1 or anti-PDL1 therapy. If patient has BRAFm melanoma, must have progressed on a BRAF/MEK inhibitor therapy as well.
– Squamous cell carcinoma of the head and neck:
c. SCC of head and neck with HPV positive or negative (as determined by local standard). Excludes primary tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.
d. Disease progression after having received at least 1 and less than 3 prior lines of systemic therapy in the metastatic setting. Must have disease progression after treatment with anti-PD1/ anti-PD-L1 therapy (either as monotherapy or in combination with chemotherapy or other therapies). Must also have disease progression on PBC regimen in recurrent or metastatic setting, or in locally advanced setting with curative intent.
– Gastric or GEJ adenocarcinoma:
e. Tumor tissue confirmed as negative for HER2 expression as per ASCO-CAP guidelines. Determined prior to enrollment by local lab assessment or other accredited
f. Disease progression after treatment with at least 2 prior lines of therapy that include PBC with or without anti-PD-1 therapy.
– Ovarian carcinoma:
g. Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
h. Documented progression at least 4 weeks after last dose of PBC and less than 6 months after last dose of PBC in the advanced / metastatic setting. Prior folate reductase alpha-targeting ADC (such as mirvetuximab soravtansine) is allowed.
– Endometrial cancer:
k. Pathologically or cytologically documented endometrial cancer, irrespective of MSI or mismatch repair status.
l. documented disease progression after at least 1 line of therapy (and maximum of 3) PBC containing systemic treatment and an anti-PD-1/ PD-L1 therapy in the advanced / metastatic setting.
– Bladder cancer:
m. Pathologically or cytologically confirmed urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is the predominant. small cell / neuroendocrine tumors are not allowed, even if mixed histology.
n. Relapsed or progressed after treatment with at least 1 (and maximum of 3) that contains anti-PD-1/anti-PD-L1 therapy in perioperative or metastatic setting. At least 1 line of therapy must contain following treatment modalities: Chemo or enfortumab vedotin. Prior FGFR-inhibitor treatment for those who are eligible are allowed. (Required treatments can be given in combination or sequentially. Prior cisplatin-based therapy or PD-1/PD-L1 given for treatment of muscle invasive urothelial carcinoma is counted as 1 line of therapy. Same regimen administered twice in different disease settings is counted as 1 line of prior therapy)
– Esophageal Carcinoma:
o. Pathologically or cytologically documented esophageal squamous cell carcinoma.
p. must have documented disease progression after receiving 2 prior lines of therapy including previous PBC with or without anti-PD-1 therapy in advanced or metastatic setting.
– Pancreatic carcinoma:
q. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma.
r. Relapsed or disease progression after 1 prior line of systemic therapy in locally advanced / metastatic setting.
– Prostate Cancer:
s. Pathologically or cytologically documented unresectable locally advanced or metastatic CRPC.
t. Adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
u. Surgically or medically castrated, with testosterone levels of <50ng/dL.
v. Documented radiographic progression for patients with measurable disease after androgen deprivation.
w. Relapsed or disease progression after at least 1 of the following: abiraterone, enzalutamide, apalutamide, or darolutamide.
x. Relapsed or disease progression after receiving at least 1 cytotoxic chemotherapy that included a taxane.
*Additional criteria may apply and will be discussed with the treating physician and research team.
Exclusion Criteria:
– Has HER2-positive gastric cancer classified by ASCO-CAP guidelines prior to enrollment.
– Has Nasopharyngeal cancer.
– Has mucosal or uveal melanoma.
– Has history of ILD/pneumonitis which required corticosteroids, or has current ILD/pneumonitis.
– Has clinically significant respiratory compromise from pulmonary illnesses including but not limited to:
a. Any underlying pulmonary disorder (i.e. pulmonary emboli within 3 months prior to cycle 1 day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, or pleural effusion).
b. any autoimmune or connective tissue, or inflammatory disorders (i.e. rheumatoid arthritis, Sjorgen’s syndrome, and sarcoidosis), where there is documented or suspicion of pulmonary involvement at time of screening.
c. Prior complete pneumonectomy.
-Is receiving chronic systemic corticosteroids of at least 10mg prednisone or equivalent, or any form of immunosuppressive therapy prior to cycle 1 day 1. Patients on bronchodilators, inhaled/topical steroids, or local steroid injections may be included in the study.
– Has history of, or evidence of current leptomeningeal disease.
– Has clinically significant corneal disease.
– Has evidence of clinically active spinal cord compression, or brain metastasis – defined as symptomatic or untreated, or requiring corticosteroid or anticonvulsant therapy to control symptoms. Patients with clinically inactive or treated brain mets who are asymptomatic may be included if they are neurologically stable for at least 4 weeks prior to cycle 1 day 1.
– Had inadequate washout period prior to Cycle 1 Day 1 as follows:
a. whole brain radiation within 28 days, or stereotactic radiation within 7 days.
b. cytotoxic chemo, other investigation agent, or other anticancer therapy within 14 days (or 5 half-lives, whichever is longer).
c. any ICI therapy within 21 days.
d. any mAbs other than ICIs, such as VEGF or anti-EGFR within 28 days.
e. Major surgery within 28 days.
f. Radiotherapy treatment to more than 30% of bone marrow, or wide field radiation within 28 days, or palliative radiation within 7 days.
g. Chloroquine or hydroxychloroquine within 14 days.
– Had prior treatment with anti-HER3 antibody, or ADC that contains extacecan derivative that is a topoisomerase I inhibitor.
– Has unresolved toxicities from previous anticancer therapy that has not resolved to at least grade 1 or baseline per CTCAE guidelines. (Subjects with Grade 2 toxicities that have not worsened for greater than 3 months prior to Cycle 1 Day 1 may be enrolled if toxicity is deemed manageable by the treating physician. These can include things such as: Chemo-induced neuropathy, fatigue, residual toxicities from prior immuno-oncology treatment: grade 1 or grade 2 endocrinopathies including hypo/hyperthyroidism, Type 1 diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation).
– History of other active malignancy within 3 years prior to Cycle 1 Day 1 except: adequately treated melanoma skin cancer and adequately treated thin primary melanoma <1m. Adequately treated intraepithelial carcinoma of the cervix. Any other curatively treated in situ disease. Early prostate cancer (T1-T2a, Gleason score </=6 and PSA <10ng/mL) not requiring treatment.
– Has uncontrolled or significant cardiovascular disorder prior to cycle 1 day 1.
– Has active HCV infection or uncontrolled HIV 1/2 infection. HIV infected patients must meet certain criteria to be deemed eligible.
– Has active HBV infection.
– Has evidence of severe or uncontrolled disease, psychiatric illness, social situation, geographical factors, substance abuse, or other factors that, in the treating physicians opinion would make the patient high-risk to participate in the study.
– Has known hypersensitivity to either drug substance or inactive ingredients in drug product.
– Female subject who is pregnant or breastfeeding or intends to become pregnant during the study.
– Has ongoing clinically relevant illness, medical condition, surgical history, lab finding or abnormality that, in the treating physician’s opinion, would pose risk to safety of the patient.
– Has previously received irinotecan treatment in advanced or metastatic disease setting.
*Additional criteria may apply and will be discussed with the treating physician and research team.
Study Contact:
Lisa Wahowske, RN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
INBRX-106: An Open-Label, Multicenter, First-in Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination with Pembrolizumab in Subjects with Locally Advanced or Metastatic Solid Tumors
Study sponsor: Inhibrx, Inc.
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: 1/2
Purpose of study: The purpose of the study is to determine the safety and tolerability of the study drug INBRX-106. INBRX-106 works by activating OX40, which is a stimulant for the immune system. If INBRX-106 works, it should stimulate your immune system, which in turn can help your body fight the tumor. This mechanism is similar to CTLA-4, PD-1 or PD-L1 blocking antibodies (called immune checkpoint inhibitors), which have been approved by the FDA for the treatment of certain tumors.
Inclusion Criteria:
– Must be age 18 or older at time of signing informed consent.
– Tumor types included:
Part 4 (study drug in combination with Pembrolizumab) – Cohort F3: non-small cell lung cancer that has had no more than 2 lines of standard therapy including at least 1 anti-PD1/L1 drug. Cohort F4: Checkpoint inhibitor naïve with confirmed Head and neck squamous cell carcinoma, or confirmed nasopharyngeal carcinoma. Must have been treated with 0-1 prior lines and HNSCC patients, minimum of 4 must provide fresh biopsies. Cohort F7 – NSCLC.
– Must have PD-L1 tests available or provide tissue for PD-L1 testing at screening to be eligible. At least 50% TPS score for Cohorts C3 and F3. At least 1% for cohort F4, and 0% + is acceptable for Cohort F7.
– Must have measurable disease by RECIST 1.1
– Adequate organ function as determined by local lab tests.
– ECOG of 0-1.
– Patients must agree to highly effective methods of contraception or abstinence during and 4 months after the last dose of study drug.
Additional criteria may apply and will be discussed with the physician and study team.
Exclusion Criteria:
– Prior exposure to OX40 agonists.
– For part 4 cohort F4 only: prior exposure to anti-PD-1/PD-L1 checkpoint inhibitors in the relapsed or metastatic setting.
– received any investigational or approved anticancer drug within 4 weeks prior to first dose of study drug. (Hormone replacement therapy is allowed).
– Radiotherapy within 2 weeks prior to first dose. 1-week washout is permitted for palliative radiation to non-CNS disease.
– Allergy to INBRX-106 or known allergies to antibodies produced from Chinese Hamster ovary cells which could suggest increased potential for hypersensitivity to study drug.
– Hypersensitivity to pembrolizumab or any of its excipients, to chemo agents, or to folic acid or vitamin B12.
– Hematologic malignancies
– For patients with NSCLC:
- cohorts F3 and F7: Received radiation therapy to lung >30Gy within 6 months prior to first dose
- F3 + F7: patients with non-squamous NSCLC with EGFR mutations or ALK gene rearrangements
- Cohort F7: unable to take folic acid or vitamin B12 supplements. Squamous histology is excluded. Mixed is allowed is the predominant type is non-squamous. Also excluded if small cell elements are present.
– Has known active CNS metastases or carcinomatous meningitis. Patients with previously treated brain mets are able to participate provided they are radiologically stable and without evidence of progression for 4 weeks, and also do not require corticosteroids for at least 14 days prior to first dose of study drug.
– Prior or concurrent malignancies. Some exclusions are allowed after discussion between physician and study medical monitor.
– Grade 3 or higher immune-related adverse event that resulted in discontinuation of prior therapy.
– Active or documented autoimmune disease that requires systemic steroids or immunosuppressive medications. (hormone replacement therapy is an exception and is allowed).
– immunodeficiency or treatment with systemic immunosuppressive medication within 7 days prior to first dose of study drug.
– Patients that received granulocyte colony-stimulating factor or erythropoietin within 14 days prior to first dose.
– history of Hepatitis B or C, or HIV.
– HIV patients must be on anti-retroviral therapy, and have controlled HIV disease at time of screening.
– Subjects with past or ongoing HCV infection are eligible if completed treatment 1 month prior to starting study drug and have negative HCV RNA test at screening.
– Clinically significant cardiac condition.
– Active interstitial lung disease, pneumonitis, or history of, requiring treatment with immunosuppressive meds or steroids.
– Pulmonary embolism within 12 weeks prior to first dose.
– Major surgery within 4 weeks prior to first dose.
– Active infection requiring systemic therapy within 4 weeks prior to first dose.
– Pregnant or nursing.
– Prior allogenic organ transplant or stem cell/bone marrow transplant.
– Live vaccine within 4 weeks prior to first dose of study drug.
– Any known documented or suspected history of substance abuse that in the opinion of the physician would interfere with the patient’s ability to adhere to study required visits and requirements.
Additional criteria may apply and will be discussed with the physician and study team.
Additional criteria may apply and will be discussed with the physician and study team.
Study Contact:
Alissa Gavenda, RN
(952) 992-5705
Alissa.Gavenda@ParkNicollet.com
STK-012: A Phase 1a/1b Study to Evaluate the Safety and Tolerability of STK-012 as a Single Agent and in Combination Therapy in Subjects with Selected Advanced Solid Tumors
Study sponsor: Synthekine, Inc.
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: I
Purpose of study: The purpose of this study is to test the safety and tolerability of the study drug STK-012 as a single drug, or in combination with other therapy. The drug works by helping to trigger the body’s immune system to attack the cancer cells, and destroying the cells so that they can’t multiply and divide.
Inclusion Criteria:
– Must be at least 18 years or older.
– Life expectancy of at least 3 months as determined by the treating physician.
– Must have measurable disease via RECIST 1.1.
– ECOG of 0 – 1.
– Adequate organ function as determined by local lab tests within 28 prior to first dose.
– Female patients of childbearing potential must have a negative serum pregnancy test within 72hrs prior to first dose of study drug, and must also agree to highly effective birth control methods during treatment, and for at least 180 days post last dose unless meeting the following criteria: Over the age of 60, postmenopausal with no menses for 1 year, and confirmed by FSH, history of hysterectomy and/or bilateral oophorectomy, or a history of bilateral tubal ligation.
– Male patients must also agree to highly effective methods of contraception and refrain from donating sperm during treatment, and for 180 days after the last dose.
– Patients must have adequate archival tissue within 24 months of screening. If archival tissue is not available, a fresh biopsy is required (unless deemed unsafe by the treating physician and discussion with the study medical monitor).
– Must have confirmed Stage IV non-squamous non small cell lung cancer.
– Patient’s tumor must be predominantly non-squamous histology. If small cell elements are present, patient will be ineligible.
– Must not have any known actionable gene mutations for which there are approved targeted therapies.
– Subjects in part E can have any level of PD-L1 expression (TPS of 0-100%), subjects in part F must have negative PD-L1 (TPS<1%) per local testing.
– Must not have received prior treatment for advanced NSQ NSCLC (Subjects that received adjuvant, neoadjuvant, or consolidation therapy are eligible for the study if the therapy was completed at least 12 months prior to recurrence or progression).
*Additional inclusion criteria may apply and will be discussed with the physician and research team*
Exclusion Criteria:
– Received systemic anticancer therapy within 3 weeks prior to first dose.
– Received radiation therapy within 2 weeks prior to first dose.
– Received prior treatment with IL-2 or IL-15 based cytokine therapy.
– Has history of pulmonary fibrosis (including pneumonitis), drug or radiation induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT.
– Currently participating in, or has participated in a study of an investigational agent or investigational device within 4 weeks prior to first dose of study drug. Subjects that entered a follow-up phase of an investigational study may participate if at least 4 weeks has passed since the last dose of previous treatment.
– Has received prior therapy with anti-PD1 or anti-PD-L1 agent, or agent directed to other receptors (such as CTLA-4, OX40, or CD137).
– Failure to recover from immune-related adverse event from previous immunotherapy. (Patients with sensory neuropathy, alopecia, or endocrinopathies that are controlled by hormone-replacement therapy, or other grade 2 or less event that in the physician’s opinion does not pose a safety risk to the patient, are eligible).
– Failure to recover from other non-immune-related toxicities from prior therapy to at least grade 2 or less.
– Known active brain mets. Patients with treated brain mets may be eligible if they are clinically stale and without need of steroid treatment for at least 14 days prior to first dose of study drug.
– Hypersensitivity of Grade 3 or higher to monoclonal antibodies, including pembrolizumab or any of its excipients.
– Known history or, or active autoimmune disease or syndrome that requires steroids or immunosuppressive agents. (patients with Vitiligo, type 1 diabetes mellitus, resolved childhood asthma, hypo- or hyperthyroidism due to autoimmune condition that doesn’t require immunosuppressive treatment, psoriasis, atopic dermatitis, or other skin condition that is managed without systemic therapy, or arthritis that is managed without systemic therapy beyond oral acetaminophen and NSAIDs are allowed).
– History of allogenic/solid tissue organ transplant.
– Clinically significant cardiovascular disease or risk factors at screening that include the following: cerebral vascular accident/stroke, or myocardial infarction, unstable angina, congestive heart failure (>/=NYHA class 2), or serious cardiac arrhythmia requiring medication. QTcF>470 on screening ECG, or congenital long QT syndrome. TdP, including hypokalemia or hypomagnesemia, history of significant or symptomatic bradycardia. Family history of sudden death or congenital long QT syndrome. Concomitant medications with known risk of Torsades De Pointe that cannot be discontinued or replaced with safe alternative within 6 half-lives before first dose of study drug.
– History of other clinically unstable/uncontrolled disorder, condition, or disease, that in the opinion of the physician, would pose a risk to patient safety, or interfere with the study evaluations, procedures, or completion.
– Serious active bacterial, viral, parasitic, or systemic fungal infections requiring systemic treatment within 30 days prior to first dose of study drug.
– Known additional malignancy that is progressing, or has required active treatment within the last 2 years (Patients with basal cell, squamous cell skin cancer, or carcinoma in situ that has undergone curative therapy are not excluded from being able to participate in the study).
– Has received a live-virus vaccine within the last 30 days prior to first dose of study drug (Seasonal flu and covid-19 vaccines that do not include live virus are permitted).
– Known history of testing positive for HIV or AIDS, or testing positive for HIV by positive serum HIV test at screening.
– Active hepatitis B or C infection at screening as confirmed by local lab tests.
– Pregnant, breastfeeding, expecting to conceive, or to father children within the duration of the study, starting at screening and through 180 days after the last dose of study drug.
*Additional criteria may apply and will be discussed with the physician and research team*
Study Contact:
Lisa Wahowske
(651) 254-1517
lisa.wahowske@parknicollet.com
XTX301-01/02-001: A First-in-Human, Multicenter, Phase 1, Open-Label Study of XTX301 in Patients With Advanced Solid Tumors
Study sponsor: Xilio Development Inc.
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: I
Purpose of study: The main purpose of this study is to determine if XTX301 is safe and well-tolerated in participants with advanced solid tumors. This is the first time XTX301 is going to be given to humans, so this study will also serve to determine the recommended XTX301 dose and schedule in later clinical studies.
Inclusion Criteria:
– Patient must be at least 18 years or older at time of consent.
– Must meet the following disease criteria:
a. Part 1A – any confirmed solid tumor that is locally advanced or metastatic that has failed standard treatments, or for which there is no standard therapy available.
b. Part 1B – Locally advanced or metastatic tumor that is any of the following: Melanoma, non-small cell lung cancer (NSCLC), Head and Neck Squamous cell, Triple-negative breast (TNBC), Cervical cancer, MSI-H/dMMR colorectal, or MSI-H/dMMR endometrial cancer.
– Patient must not have received prior anticancer therapy for at least 28 days prior to starting study treatment, and must have returned to baseline or grade 1 for any side effects from previous therapy.
– Must have ECOG of 0-2.
– Patient must have adequate organ function as determined by local lab tests.
– For Part 1B only: patients must be willing to undergo a tumor biopsy before starting, and while on study treatment.
– Women of Childbearing Potential (WOCBP) must be willing to abstain from sexual activity, or use highly effective contraception. Additionally, must also have a negative serum pregnancy test at the time of study enrollment and before each dose of study drug.
– Additional criteria may apply and will be discussed with the physician and study team.
Exclusion Criteria:
– Must not have had previous treatment with IL-12 therapy
– Patients with known liver metastasis are excluded, unless previous discussion between treating physician and study medical monitor approves the patient to enroll.
– Concurrent anticancer therapy, immune therapy, or cytokine therapy, or other antineoplastic therapy during the study.
– History of significant pulmonary disease, interstitial lung disease or pulmonary fibrosis.
– History of significant heart disease, uncontrolled hypertension, congestive heart failure, or myocarditis.
– Possible area of non-disease related necrosis, such as an active ulcer, a non-healing wound, or intercurrent bone disease.
– Has active central nervus metastases, or carcinomatous meningitis.
– Active autoimmune disease that required therapy in the past 2 years, including use of corticosteroids, or immunosuppressive drugs.
– Has an active infection that requires systemic therapy within 4 weeks prior to receiving study drug.
– Has a history of Grade 3 or higher immune-related toxicities from prior immunotherapy unless it resolved within 14 days.
– Has had history of severe hypersensitivity to monoclonal antibodies
– Is pregnant or breastfeeding.
– Has active hepatitis B or C infection.
– Has had prior gene therapy treatment, organ transplant, or hematopoietic stem-cell transplant.
– Is currently using or has received another investigational drug or device within 4 weeks prior to starting study drug.
– Has received a live or live-attenuated vaccine within 4 weeks prior to first dose.
– Additional exclusion criteria may apply and will be discussed with the physician and study team.
Study Contact:
Alissa Gavenda, RN
(952) 993-6705
Alissa.Gavenda@ParkNicollet.com
