A Study of TAVO412 in Patients With Cancer
Study Details
Study Description
Brief Summary
TAVO412 Phase 1 is an open-label, non-randomized, 2-part Phase I study to examine the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of TAVO412. Part 1 will utilize a standard 3 + 3 design to determine the MTD/RP2D of TAVO412 in subjects with advanced or metastatic solid tumors who progressed on prior approved standard of care therapy. Part 2 will further evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacologic activity of TAVO412 in a new set of subjects with advanced or metastatic gastric cancer, non-small cell lung cancer (NSCLC), or subjects of other solid tumor types with best clinical responses (e.g., CR > PR > SD) from Part 1 that progressed on prior approved standard of care therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is an open-label, non-randomized, Phase I study to determine the safety and tolerability, define the MTD/RP2D, and assess the preliminary efficacy of TAVO412 in subjects with advanced or metastatic solid tumors who progressed on prior approved standard of care therapy. Subjects will receive TAVO412 at the tested dose intravenously on Day 1, 8, 15, and 22 in Cycle 1 and will continue this weekly treatment schedule for all future cycles.
The study will be conducted in 2 parts:
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Part 1 - Dose Escalation will determine the MTD and/or RP2D of TAVO412, which includes defining the optimal dose administration schedule.
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Part 2 - Cohort Expansion will evaluate the recommended dose and administration schedule (MTD/RP2D) determined in Part 1 in a new set of subjects with advanced or metastatic gastric cancer, non-small cell lung cancer (NSCLC), or subjects of other solid tumor types with best clinical responses (e.g., CR > PR > SD) from Part 1 that progressed on prior approved standard of care therapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Part 1 Cohort 1 IV infusion of TAVO412 |
Drug: TAVO412
Biologic
|
| Other: Part 1 Cohort 2 IV infusion of TAVO412 |
Drug: TAVO412
Biologic
|
| Other: Part 1 Cohort 3 IV infusion of TAVO412 |
Drug: TAVO412
Biologic
|
| Other: Part 1 Cohort 4 IV infusion of TAVO412 |
Drug: TAVO412
Biologic
|
| Other: Part 1 Cohort 5 IV infusion of TAVO412 |
Drug: TAVO412
Biologic
|
| Other: Part 2 Cohorts IV infusion of TAVO412 |
Drug: TAVO412
Biologic
|
Outcome Measures
Primary Outcome Measures
- Safety and Tolerability of TAVO412 according to Adverse Events and Number of Participants With Dose Limiting Toxicity (DLT) using National Cancer Institute CTCAE v5.0 [Approximately 12 months]
According to the frequency, duration, and severity of Adverse Events (AEs). The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury. The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 has a minimum value of Grade 1, or mild, and a maximum value of Grade 4, Life-threatening; pressor or ventilatory support indicated. All DLTs will be assessed by the investigator using National Cancer Institute CTCAE v5.0.
Secondary Outcome Measures
- Maximum Serum Concentration (Cmax) of TAVO412 [Approximately 12 months]
The Cmax is the maximum observed serum concentration of TAVO412.
- Time to Reach Maximum Observed Serum Concentration (Tmax) of TAVO412 [Approximately 12 months]
The Tmax is defined as time to reach maximum observed serum concentration of TAVO412.
- Minimum Serum Concentration (Cmin) of TAVO412 [Approximately 12 months]
The Cmin is the minimum observed serum concentration of TAVO412.
- Area Under the Serum Concentration-Time Curve From 0-1 (AUC[t0-t1]) [Approximately 12 months]
The AUC(t0-t1) is the area under the serum TAVO412 concentration-time curve from time t0 to t1.
- Overall Response Rate (ORR) [Approximately 12 months]
ORR is defined as the percentage of subject having complete response (CR) or partial response (PR).
- Duration of Response (DOR) [Approximately 12 months]
DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression.
- Progression-Free Survival (PFS) [Approximately 12 months]
PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression.
- Duration of Disease Control (CR, PR, and SD) [Approximately 12 months]
Duration of disease control is defined as the sum of PFS followed by maintenance.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male/Female aged 18 (at the time of screening) or older.
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Willingness to provide written informed consent for the study.
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Locally relapsed or refractory disease; locally advanced disease must not be amenable to resection with curative intent.
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Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
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Presence of measurable disease based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
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Part 1: Subjects with advanced or metastatic solid tumors who progressed on prior approved standard of care therapy.
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Part 2: A new set of subjects with advanced or metastatic gastric cancer, non-small cell lung cancer (NSCLC), or subjects of other solid tumor types with best clinical responses (e.g., CR > PR > SD) from Part 1 that progressed on prior approved standard of care therapy.
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For subjects with Gastric Cancer: histologically confirmed Gastric or Gastro-Esophageal Junction Carcinoma (including adenocarcinoma arising from the lower esophagus). If multiple eligible patients exist, preference will be given to enroll subjects with cMet (tyrosine-protein kinase Met) or EGFR mutations, over-expression, or gene amplification.
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For subjects with NSCLC: histologically or cytologically confirmed tumor must be NSCLC with EGFR and/or cMet mutations, over-expression, or gene amplification.
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Part 2: Willingness to undergo pretreatment and on-treatment tumor biopsies (core or excisional).
Note: A baseline biopsy obtained for other purposes (i.e., not a protocol-defined procedure) before signing consent may be utilized if the subject has not had any intervening systemic therapy from the time of the biopsy to the start of treatment (i.e., Cycle 1 Day 1), and if a minimum of 20 slides or preferably 1 tissue block can be submitted.
Note: If a subject is scheduled to have a tumor biopsy for the purposes of this study and it is subsequently determined that tumor tissue cannot safely be obtained, then the subject may still enroll in the study. The subject may be replaced within the cohort.
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For both Part 1 & Part 2, subjects willing to consent to collection of additional blood or tissue samples for exploratory biomarker or genomic analysis purposes.
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ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1.
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Female subjects of child-bearing potential (defined as women who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not postmenopausal, defined as ≥ 12 months of amenorrhea) must have a negative serum pregnancy test at screening.
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All female subjects of child-bearing potential must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 60 days after the last dose of study drug.
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All male subjects must agree to take appropriate precautions to avoid pregnancy with a partner (with at least 99% certainty) from screening through 90 days after the last dose of study drug. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subjects and their understanding confirmed.
Exclusion Criteria:
• Laboratory and medical history parameters not within the protocol-defined range. If the screening laboratory tests below were conducted > 7 days before treatment initiation, they will need to be repeated on Day 1 before initiation of treatment.
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Absolute neutrophil count < 1.5 × 109/L.
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Platelets < 100 × 109/L.
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Hemoglobin < 9 g/dL or < 5.6 mmol/L.
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Serum creatinine > 1.5 × institutional upper limit of normal (ULN), OR using CKD-EPI formula as the method for measurement
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Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≥ 2.5 × ULN.
Note: Subjects with 1) bone metastases and 2) no hepatic parenchymal metastases on screening radiographic examinations may enroll if the alkaline phosphatase ≤ 5 × ULN. Subjects with 1) bone metastases and/or 2) hepatic parenchymal metastases on screening radiographic examinations may enroll if the alkaline phosphatase is ≤ 5 × ULN only with medical monitor approval.
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Total bilirubin ≥ 1.5 × ULN unless conjugated bilirubin ≤ ULN (note: conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then direct bilirubin must be < 40% of total bilirubin.
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International normalized ratio, prothrombin time, or activated partial thromboplastin time > 1.5 × ULN.
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Transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony- stimulating factor, or recombinant erythropoietin) within 14 days before study Day 1.
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Receipt of anti-cancer medications or investigational drugs within the following intervals before the first administration of study drug:
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≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis as a result of treatment. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval.
Note: Bisphosphonates and denosumab are permitted concomitant medications.
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≤ 28 days for prior immunotherapy or persistence of active cellular therapy (i.e., chimeric antigen receptor T-cell therapy; other cellular therapies must be discussed with medical monitor to determine eligibility).
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≤ 28 days for a prior monoclonal antibody used for anticancer therapy with the exception of denosumab.
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≤ 7 days for immune-suppressive-based treatment for any reason. Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted.
Note: The use of physiologic corticosteroid replacement therapy may be approved after consultation with the medical monitor.
- ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational agents or devices. For investigational agents with long half-lives (e.g., > 5 days), enrollment before the fifth half-life requires medical monitor approval.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting therapy.
Note: Subjects with stable chronic AEs (≤ Grade 2) not expected to resolve (such as neuropathy and alopecia) are exceptions and may enroll with medical monitor approval.
Note: Subjects with a history of any grade immune-related ocular AEs will be excluded.
Note: Subjects with a history of a Grade 3 or higher immune-related AE from prior immunotherapies are excluded from the dose escalation portion of the study.
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Receipt of a live vaccine within 30 days of planned start of study drug. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; COVID booster vaccines are permitted ≥ 4 weeks post; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.
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Active autoimmune disease that required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Note: Subjects who have not required systemic treatment in the past 2 years should discuss their case with medical monitor to determine eligibility.
Note: Subjects with hyper/hypothyroidism are eligible to participate. Note: Replacement and symptomatic therapies (e.g., levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered a form of systemic treatment and are allowed.
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Known active CNS metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided that they are stable (without evidence of progression by imaging for at least 28 days before the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases or CNS edema, and have not required steroids for at least 14 days before the first dose of study drug.
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Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the subject has been disease-free for > 1 year, after treatment with curative intent.
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Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
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History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 470 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is > 470 milliseconds, the subject may enroll if the average QTc for three ECGs is < 470 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded.
Note: QTc prolongation due to pacemaker may enroll if the JTc is normal or with medical monitor approval.
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Active infection requiring systemic therapy, including COVID-19.
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Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation. Hepatitis B virus DNA and HCV RNA must be undetectable. Subjects cannot be positive for HBV DNA, HCV RNA, hepatitis B surface antigen, or anti-hepatitis B core antibody, without approval from the medical monitor.
Note: Subjects with no prior history of hepatitis B infection who have been vaccinated against hepatitis B and who have a positive antibody against hepatitis B surface antigen test as the only evidence of prior exposure may participate in the study.
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Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
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Known allergy or reaction to any component of study drug or formulation components.
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Is a female who is pregnant or breast feeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 60 days after the last dose of study drug OR;
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Is a male who is expected to father children within the duration of the study, starting with the screening visit through 90 days after the last dose of study drug.
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Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study.
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Inability to comprehend or unwillingness to sign the informed consent form (ICF).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Tavotek Biotherapeutics
Investigators
- Principal Investigator: Deborah Doroshow, MD, MOUNT SINAI HOSPITAL
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 59870003