AMG193-20220127: A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors.
Principal Investigator: Tim Larson, MD
Study sponsor: Amgen, 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, tolerability, and to determine the maximum tolerated dose of the study drug AMG 193, or the maximum dose of combination of AMG 193 + IDE397 in adult patients with metastatic or locally advanced MTAP-null solid tumors. This study is split into Part 1 and Part 2. Part 1 is looking at any MTAP-null solid tumors, and Part 2 is looking at Non-small cell lung cancer MTAP-null tumors. AMG 193 is thought to work with the DNA change in your cancer cells to inhibit growth and to kill the cancer cells.
Inclusion Criteria:
– Must be at least 18 years or older.
– Must have evidence of MTAP-null or MTAP deletion as determined by lab testing.
– Advanced or metastatic tumor for which there is no curative treatment
Part 1: Any MTAP-null or MTAP deletion solid tumor that has failed standard therapy.
Part 2: MTAP-null or MTAP deletion Non-small cell lung cancer with progression after 1 to 2 lines of prior therapy. Must have had at least PD1 or PD-L1 inhibitor and platinum based chemo, or targeted therapy and chemo if genetic mutations identified (such as EGFR, ALK, MET, RET, ROS1, KRASg12c, etc).
– Ability to swallow oral study drug pill.
– Must have measurable disease according to RECIST 1.1
– Have an ECOG of 0-1.
– Adequate organ function as determined by local lab testing.
– Minimum life expectancy of 12 weeks.
– Archival tissue block must be available to be reviewed by the study lab. (For Part 1 backfill, patient must undergo fresh biopsy during screening, or archival tissue obtained within 6 months prior to study start.)
– Additional criteria may apply and will be discussed with the physician and research team.
Exclusion Criteria:
– Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastasis, or leptomeningeal disease. Patients with treated brain mets must have been treated at least 4 weeks prior to study start, and meet the following criteria: stable or improving neurological symptoms, stable or decreased doses of corticosteroids for at least 14 days prior.
– History of other malignancy within the last 2 years (with the following exceptions: malignancy treated with curative intent and is low risk for recurrence, adequately treated non-melanoma skin cancer or lentigo maligna, adequately treated cervical carcinoma in situ, breast ductal carcinoma in situ, urothelial papillary noninvasive carcinoma, or carcinoma in situ without evidence of disease).
– Evidence of current interstitial lung disease, pneumonitis, or prior history of interstitial lung disease, or non-infectious pneumonitis within 12 months prior to study start.
– Active infection requiring systemic treatment within 7 days prior to day 1 of study.
– Covid-19 infection. Minimum of 10 days must have passed after symptom onset.
– History of arterial thrombosis within 3 months prior to first dose.
– Myocardial infarct, Congestive heart failure, unstable angina, or cardiac arrhythmia requiring medication within 6 months prior to first dose.
– GI disease causing inability to take oral medication, malabsorption syndrome, gastric/jejunal tube feeds, or uncontrolled inflammatory GI disease (i.e. Crohns, or ulcerative colitis, etc.)
– History of bowel obstruction, abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to study start.
– History of solid organ transplant
– Short or long QT syndrome.
– Major surgery within 21 days prior to first dose
– Any other anti-tumor therapy within 28 days prior to study day 1,
– Prior treatment with an MAT2A inhibitor or PRMT5 inhibitor.
– Prior radiation to >25% of bone marrow
– Therapeutic or palliative radiation therapy within 1 week of study day 1 (or brain mets within 4 weeks prior to C1D1). Patients must have recovered from radiotherapy related toxicity.
– Live vaccine within 4 weeks prior to study drug administration.
– Prescription medications known to be strong CYP3A4/5 inducers or inhibitors.
– Unresolved toxicities from prior anti-cancer therapies.
– Is currently receiving another investigation study drug or device or less than 21 days since ending other study drug or device treatment.
– Hepatitis B or C infection.
– Breastfeeding female subjects which plan to become pregnant while on study through 6 months post last dose.
– Women of childbearing potential (WOCBP) with positive serum pregnancy test 7 days prior to day 1.
– Male subjects with female partners of childbearing potential that are unwilling to use highly effective methods of contraception while on study through 6 months after the last dose.
– Male subjects unwilling to refrain from donating sperm while on study drug through 6 months after the last dose.
– Any history or evidence of other clinically significant disorder, condition, or disease that in the opinion of the physician would interfere with the subjects ability to perform study procedures.
– Additional criteria may apply and will be discussed with the physician and research team.
Study Contact:
Lisa Wahowske, RN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
DB1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors
Principal Investigator: Tim Larson, MD
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
Nimbus 1150-101: A Phase 1/2, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of NDI-101150 Administered as Monotherapy or in Combination with Pembrolizumab in Patients with Solid Tumors
Principal Investigator: Kurt Demel, MD
Study Sponsor: Nimbus Saturn Inc.
Location: HealthPartners Cancer Center at Regions Hospital
Phase of Study: I
Purpose of study: The purpose of the study is to look at how effective the study drug NDI-101150 is at treating certain cancer types when it is given as a single drug, or in combination with pembrolizumab (keytruda). The drug works by blocking a protein called HPK1, and this can potentially help the immune system to better recognize and destroy cancer cells. The study is made up of a dose escalation phase, where any solid tumors are accepted, and a dose expansion phase, where only select tumor types are eligible.
Inclusion Criteria:
– Must be 18 years or older at time of signing consent.
– Must have measurable disease via RECIST 1.1.
– Must have recovered from prior therapy (be at Grade 1 or baseline).
– ECOG of 0 – 1.
– Adequate organ function as determined by screening lab tests.
– Female patients that are women of child-bearing potential (WOCBP) must agree to using highly effective contraceptive methods while on study and must have negative serum or urine pregnancy test within 48hrs prior to Cycle 1 Day 1 of study treatment.
– Must be able to swallow study medication.
– Be willing to avoid sun exposure, wear protective clothing, and/or apply sunscreen if sun exposure is unavoidable.
– For Dose Escalation portion of the study: must have advanced or metastatic solid tumors for which no standard therapies are available or must be refractory to standard therapy.
The Following inclusion criteria are for the dose expansion phase, and are in addition to the criteria listed above:
– Must be willing to consent to required tissue biopsy.
– Must have advanced or metastatic Gastric/Gastroesophageal junction, Non-small cell lung cancer, or Renal Cell Carcinoma for which there is no standard therapy available.
– Additional criteria may apply and will be discussed with the physician and study team.
Exclusion Criteria:
– Had a previous solid organ or hematopoietic stem cell transplant.
– Central Nervous System disease that is previously untreated or requires steroids or other intervention.
– Prior anti-cancer treatment that includes the following: Systemic anticancer treatment – chemotherapy, antibody or other anticancer therapy less than 4 weeks prior to first dose of study treatment. Radiation therapy, stereotactic body radiation, chemoembolization, small molecule therapy or targeted therapies.
– Significant cardiovascular disease: myocardial infarct/stroke, or unstable angina within 3 months prior to study treatment, Congestive Heart Failure, uncontrolled hypertension, or history of significant ventricular arrhythmias.
– History of severe immune-related adverse events that led to stopping of prior immunotherapy.
– History of severe hypersensitivity reaction to treatment with monoclonal antibodies.
– If patient requires corticosteroids >10mg/day prednisone or equivalent within 14 days prior to day 1. (Some exceptions may apply
– History of lung disease, pneumonitis, or pneumonia on chest scan within the last 6 months.
– Major surgery within 4 weeks prior to starting study drug, or if patient has not recovered from effects of the prior surgery.
– Uncontrolled active infection that requires IV antibiotics, antiviral, or antifungal medication within 14 days prior to study treatment.
– Known additional active malignancy that is requiring treatment (excluding basal cell, or squamous cell skin cancer, or other cancer for which patient has been disease free for more than 2 years).
– Active HIV infection, or Hepatitis B or C infection.
– Known current alcohol or drug abuse.
– unstable or uncontrolled condition, psychiatric illness, or abnormal lab finding that, in the opinion of the physician, would increase the risk to the patient.
– Prior treatment with an HPK1 inhibitor.
– Taking any contraindicated medications that cannot be discontinued prior to starting study drug.
– Additional criteria may apply and will be discussed with the physician and study team.
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(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
Principal Investigator: Jayanthi Vijayakumar, MD
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
