Study of the Monoclonal Antibody IMT-009 in Patients With Advanced Solid Tumors or Lymphomas

Eligibility Criteria

• 1. Males and females ≥18 years of age at the time of consent
• 2. Patients who have histologically or cytologically-documented, unresectable locally advanced, or metastatic solid malignancy or designated lymphoma that is progressing or has failed the therapies listed below or who are intolerant of or are ineligible for or refuse standard of care therapy as detailed below.
• * Patients previously pre-treated with a checkpoint inhibitor must be anti-PD-L1 relapsed/refractory defined as having clear evidence of radiologic or clinical progression while on or within 4 months of their last anti-PD-L1 dose.
• * There is no limit to the number of prior treatment regimens a patient may have had prior to enrollment.
• * Non-small cell lung cancer (NSCLC) - squamous or non-squamous:
• * Must have received prior chemotherapy and a checkpoint inhibitor (either sequentially or in combination) per PD-L1 status
• * Must not have a documented EGFR, ALK, ROS, RET, BRAFV600E, Met exon 14 skipping, KRAS mutation
• * Head and neck squamous cell carcinoma (HNSCC) HPV+ or -:
• * Must have received prior treatment with a platinum-based chemotherapy and a checkpoint inhibitor (either sequentially or in combination) per PD-L1 status
• * Triple negative breast cancer (TNBC):
• * Must have received prior treatment with chemotherapy (anthracycline, and/or taxanes, and/or platinum, and/or gemcitabine); sacituzumab govitecan; a checkpoint inhibitor if PD-L1+; a PARPi for patients with gBRCA mutations
• * Cutaneous squamous cell carcinoma:
• * Must have received prior treatment with a checkpoint inhibitor
• * Hormone receptor positive (HR+) breast cancer:
• * Small bowel carcinoma:
• * Must have received prior treatment with at least one 5FU or capecitabine based regimen (such as but not limited to FOLFOX, FOLFIRI or CAPOX) with or without bevacizumab, and a PD1/PD-L1 inhibitor alone or in combination with CTLA4 inhibitor (for MSI-H or dMMR tumors)
• * Esophageal cancer:
• * Must have received prior treatment with a platinum-based chemotherapy and a checkpoint inhibitor (either sequentially or in combination per PD-L1 status), and an anti-HER2 agent for patients with known HER2 overexpressing tumors
• * Colorectal cancer (MSS \& MSI-H/dMMR):
• * Must have received at least one 5FU chemotherapy-based regimen, with bevacizumab or cetuximab/panitumumab, and / or a PD1/PD-L1 (single agent or combination with CTLA4) for dMMR/MSI-H tumors
• * For patients with known BRAF V600E mutation: must have received prior treatment with a combination of encorafenib and cetuximab or panitumumab
• * Histologically confirmed diffuse large B cell lymphoma (DLBCL)
• * Must have received at least 2 prior lines of therapy including prior treatment with chemotherapy and an anti-CD20 antibody (ie, CHOP)
• * Must be ineligible or refuse therapies with demonstrated clinical benefit such as for example CAR-T or autologous stem cell transplant
• * Hodgkin lymphoma:
• * Burkitt lymphoma:
• * Must have received at least 2 prior lines of therapy
• * Must be ineligible or refuse therapies with demonstrated clinical benefit
• * Follicular lymphoma:
• * Must have received 3 prior lines of therapy, and must have received rituximab and chemotherapy
• 3. Patients with solid tumors have measurable disease based on RECIST 1.1. In hematological malignancies LYRIC/Lugano will be used.
• 4. In defined cohorts must have confirmed positive expression of CD161. Patients must have an available archival biopsy sample or agree to have a fresh biopsy obtained to confirm positivity and must agree to a mandatory newly obtained on-treatment biopsy.
• 1. Must have histologically or cytologically-documented, unresectable, locally-advanced or metastatic MSS CRC with documented IHC for MMR and/or DNA for MSI consistent with MSS CRC.
• 2. Eligible for treatment with fruquintinib according to the FDA-approved USPI
• 3. Must have received no more than 3 prior lines of therapy, consisting of prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy
• 4. Body weight ≥40kg
• 1. Any prior Grade 4 immune-mediated adverse event (imAE) or Grade 3 imAE requiring steroid treatment (\>10 mg/day prednisone or equivalent dose for more than 12 weeks) while receiving immunotherapy that has been documented within the 12 months prior to enrollment.
• 2. Unresolved toxicity higher than Grade 1 CTCAE v 5 (or higher) attributed to any prior therapy/procedure at screening, except for alopecia.
• 3. Prior history of serious hypersensitivity reaction to treatment with a monoclonal antibody
• 4. Patients who are currently pregnant or breastfeeding
• 5. Use of other investigational drugs (drugs not marketed for any indication) within 14 days or at least 5 half-lives (whichever is shorter) before investigational enrollment (Day 1, Cycle 1 dosing)
• 6. Patient with history of malignancy (other than the one for which he/she participates in the study or than basal cell carcinoma definitively resected, or other in situ cancers) - unless the patient has undergone curative therapy with no evidence of that disease for 3 years
• 7. Patients currently receiving cancer therapy (ie, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery, and/or tumor embolization) or expected to require any other form of antineoplastic therapy while on study.
• 8. Patients with active, known or suspected autoimmune disease requiring systemic treatment (corticosteroids or other active immunosuppressive medications) within the past 6 months - with the exclusion of vitiligo, resolved asthma/atopia or alopecia areata; hypothyroidism stable on hormone replacement.
• 9. Known CNS metastases (unless clinically stable for at least 4weeks prior to enrollment and off steroids for at least 7 days- exceptions above for physiologic replacement doses of hydrocortisone)
• 10. Myocardial infarction, symptomatic congestive heart failure (NYHA\> Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of screening
• 11. Patient has history of or current HIV, Hepatitis B or C infection, even if not active and/or controlled
• 1. Serum electrolytes, potassium, calcium, or magnesium levels outside of the normal laboratory reference range and clinically significant in the investigator's judgment
• 2. Serum creatinine \>1.5 × ULN or creatinine clearance \<60 L/min.
• 3. Urine dipstick protein ≥2+ or 24-hour urine protein ≥1.0 g/24-h
• 4. Uncontrolled hypertension, defined as: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg despite optimal medical management
• 5. History of thromboembolic events
• 6. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction or coronary artery bypass surgery, symptomatic congestive heart failure (New York Heart Association \[NYHA\] Classification \> Class II), severe or unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of screening
• 7. Patient has history of or current human immunodeficiency virus (HIV), or hepatitis B infection, even if not active and/or controlled. Prior hepatitis C virus (HCV) infection treated with a full course of curative intent antivirals with an undetectable viral load (below the lower limit of detection) are eligible
• 8. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks prior to the first dose of study drug and while on study
• 9. Planned major surgery within 2 weeks prior to study start or during the study