Brief Title: A Study of TRK-950 in Combinations With Anti-Cancer Treatment Regimens in Patients With Advanced Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Frequency of patients experiencing treatment emergent adverse events as assessed by CTCAE v5.0

Primary Outcome 1 - Timeframe: through study completion, an average of 1 year

Primary Outcome 2 - Measure: Frequency of patients experiencing adverse events of special interest (AESIs)

Primary Outcome 2 - Timeframe: through study completion, an average of 1 year

Primary Outcome 3 - Measure: Blood pressure

Primary Outcome 3 - Timeframe: through study completion, an average of 1 year

Primary Outcome 4 - Measure: Heart rate

Primary Outcome 4 - Timeframe: through study completion, an average of 1 year

Primary Outcome 5 - Measure: Respiratory rate

Primary Outcome 5 - Timeframe: through study completion, an average of 1 year

Primary Outcome 6 - Measure: Temperature

Primary Outcome 6 - Timeframe: through study completion, an average of 1 year

Primary Outcome 7 - Measure: Weight

Primary Outcome 7 - Timeframe: through study completion, an average of 1 year

Primary Outcome 8 - Measure: Height

Primary Outcome 8 - Timeframe: through study completion, an average of 1 year

Primary Outcome 9 - Measure: Performance status using Karnofsky performance status criteria

Primary Outcome 9 - Timeframe: through study completion, an average of 1 year

Primary Outcome 10 - Measure: QTc interval determined from 12-lead Electrocardiogram

Primary Outcome 10 - Timeframe: through study completion, an average of 1 year

Primary Outcome 11 - Measure: QRS interval determined from 12-lead Electrocardiogram

Primary Outcome 11 - Timeframe: through study completion, an average of 1 year

Primary Outcome 12 - Measure: Frequency of patients with laboratory abnormalities (Complete Blood Count, Coagulation, Urinalysis and Serum Chemistry)

Primary Outcome 12 - Timeframe: through study completion, an average of 1 year

CONDITION

• Solid Tumor
• Colorectal Cancer
• Cholangiocarcinoma
• Bladder Cancer
• Ovarian Cancer
• Gastric Cancer
• Palpable Subcutaneous Malignant Lesions
• Renal Cell Carcinoma
• Melanoma
• Epithelial Ovarian Cancer
• Primary Peritoneal Cancer
• Fallopian Tube Cancer

ELIGIBILITY

Inclusion Criteria:
Histologically confirmed solid malignancy for which the following treatment regimens are warranted:

- Arm A. Colorectal Cancer with no prior history of treatment with Irinotecan alone or in combination: FOLFIRI as standard of care

- Arm B. Cholangiocarcinoma, Bladder Cancer with no prior history of treatment with Gemcitabine alone or in combination: Gemcitabine / Cisplatin as standard of care

- Arm C and Expansion Cohort 1. Ovarian Cancer who have relapsed at least 6 or more months after completion of a previous platinum-based therapy and have no prior history of treatment with gemcitabine alone or in combination: Gemcitabine / Carboplatin as standard of care

- Arm D and Expansion Cohort 2. Gastric Cancer including Gastroesophageal Junction with no prior history of treatment with Ramucirumab, Paclitaxel or any Taxane class drug: Ramucirumab / Paclitaxel as standard of care

- Arm E. Solid Tumors: Eligible for PD1 Inhibitor (Nivolumab or Pembrolizumab) monotherapy as standard of care according to the approved drug label by the relevant regulatory authority

- Arm F. Locally advanced or metastatic disease in a cancer with at least one palpable subcutaneous malignant lesion (≤ 2 cm in diameter) for treatment with TRK-950 and Imiquimod cream (US Sites Only)

- Arm G. Renal Cell Carcinoma with no prior history of treatment with Bevacizumab alone or in combination: Bevacizumab for use in a fourth line or later treatment

- Arm H. Melanoma patients who progressed while taking Nivolumab, Pembrolizumab, or Ipilimumab, within the last 6 months prior to cycle 1 day 1

- Arm J. Colorectal Cancer patients who progressed on FOLFIRI or any other Irinotecan-containing therapy regimen within the last 6 months prior to cycle 1 day 1

- Arm K. (US Sites Only). Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 2 prior treatment lines who have recurred > 6 months after most recent platinum-based chemotherapy and who are eligible for gemcitabine, carboplatin, and Bevacizumab as standard of care for dosing of TRK-950(Lower-dose)
Arms M and O. Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 5 prior treatment regimens, as defined below and who are eligible for topotecan or pegylated liposomal doxorubicin as standard of care for dosing of TRK-950(Lower-dose)
Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response, and then progressed between 3 months and less than or equal to 6 months after the last date of platinum.

- Patients who have received 2 to 5 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum.

- Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy

- Arm Q. Gastric Cancer including GEJ cancer with only 1 prior treatment regimen, which recurred during or within 4 months after frontline treatment, and no prior history of treatment with Ramucirumab, Paclitaxel or any Taxane class drug for metastatic disease: eligible to receive Ramucirumab/Paclitaxel as standard of care (Lower-dose)

- Arm R. Clear cell renal cell carcinoma with no prior history of treatment with Bevacizumab alone or in combination: Bevacizumab for use in a fourth line or later treatment. (Lower-dose)

- Primary or metastatic tumors measurable per RECIST v1.1 on CT scan or by calipers (subcutaneous lesions)

- Karnofsky performance of ≥70

- Life expectancy of at least 3 months

- Age ≥ 18 years

- Signed, written IRB-approved informed consent
Exclusion Criteria:
Laboratory values or medications that are contraindicated in the selected standard of care treatment regimens

- New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG

- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Prophylactic antibiotics are acceptable.

- Pregnant or nursing women

- Treatment with radiation therapy within 2 weeks, or treatment with surgery, chemotherapy, immunotherapy, targeted therapy or investigational therapy within four weeks prior to initiation of study treatment (6 weeks for nitrosoureas or mitomycin C, and 2 weeks or 5 half-lives whichever is longer for TKIs).

- Unwillingness or inability to comply with procedures required in this protocol

- Known active infection with HIV, hepatitis B, hepatitis C

- Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor

- Patients who are currently receiving any other investigational agent

- Any contraindicated condition or drug which would make the patient ineligible for the respective treatment regimen that is to be used in combination with TRK-950 (for example, autoimmune disorders for nivolumab or pembrolizumab treatment) as described in the Full Prescribing Information

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 602 358 8324

Email: vbauernschub@td2inc.com

LOCATION