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

Toray Industries

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: Pembrolizumab; Drug: Paclitaxel; Drug: PLD; Drug: Ramucirumab; Drug: Carboplatin; Drug: Leucovorin; Biological: TRK-950; Drug: Nivolumab; Drug: Imiquimod Cream; Drug: Cisplatin; Drug: Gemcitabine; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03872947

950P1V02

Details and patient eligibility

About

The main purpose of this study is to establish the safety and the recommended dose of TRK-950 in combination with FOLFIRI, Gemcitabine / Cisplatin, Gemcitabine / Carboplatin, Ramucirumab / Paclitaxel, PD1 inhibitors (Nivolumab or Pembrolizumab), and Imiquimod Cream, Bevacizumab, Gemcitabine / Carboplatin / Bevacizumab, Pegylated liposomal doxorubicin (PLD), Carboplatin / PLD / Bevacizumab and Paclitaxel for selected advanced solid tumors.

Full description

This study is an open-label, Phase 1b study evaluating TRK-950 in combination with 1) FOLFIRI or 2) Gemcitabine / Cisplatin or 3) Gemcitabine / Carboplatin or 4) Ramucirumab/Paclitaxel or 5) PD1 inhibitors (Nivolumab or Pembrolizumab) or 6) Imiquimod Cream for subcutaneous lesions 7) Bevacizumab 8) Gemcitabine / Carboplatin / Bevacizumab, 9)PLD, 10) Carboplatin / PLD / Bevacizumab or 11) Paclitaxel in Patients with Selected Advanced Solid Tumors. The objectives of this study are to determine the safety, tolerability, MTD, recommended Phase 2 dose (RP2D), PK, and preliminary anti-tumor activity of TRK-950 when used in combination with other treatment regimens.

Enrollment: 138 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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. 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. 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

• Arm 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

  • 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

• 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.

• Arm S. Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 2 prior treatment lines who have recurred > 182 days after most recent platinum-based chemotherapy and who are eligible for carboplatin, PLD, and bevacizumab as standard of care

  • The histological subtypes of the carcinoma that qualify for enrollment include serous adenocarcinoma, endometrioid adenocarcinoma, carcinosarcoma of the ovary, or adenocarcinoma not otherwise specified (NOS)
  • Patients with or without the breast cancer susceptibility 1/2 (BRCA1/2) mutations are eligible, provided that patients with the BRCA1/2 mutations have previously received PARP inhibitor treatment

• Arm T. Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer with ≤ 5 prior treatment regimens, or as defined below, and who are eligible for paclitaxel as standard of care

  • 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 (complete response/remission (CR) or partial response/remission (PR), and then progressed between 90 days to less than 183 days after the last date of platinum.
  • Patients who have received multiple lines of platinum therapy must have progressed on the latest platinum, or within 183 days after the date of the last dose of the latest platinum
  • Patients with or without the BRCA1/2 mutations are eligible, provided that patients with the BRCA1/2 mutations have previously received PARP inhibitor treatment
  • Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
  • The histological subtypes of the carcinoma that qualify for enrollment include serous adenocarcinoma, endometrioid adenocarcinoma, carcinosarcoma of the ovary, or adenocarcinoma not otherwise specified (NOS)

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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138 participants in 15 patient groups

Arm A: TRK-950 + FOLFIRI

Experimental group

Description:

* Colorectal Cancer * TRK-950 will be administered intravenously (IV) on days 1, 8, 15, and 22 of a 28-day cycle. On days 1 and 15 Irinotecan will be administered IV. Leucovorin will be infused to match the duration of the irinotecan infusion. 5-FU will be administered as IV bolus, followed by TRK-950 administration. After the TRK-950, 5-FU will be administered by a continuous infusion.

Treatment:

Drug: Irinotecan

Drug: 5-FU

Biological: TRK-950

Biological: TRK-950

Drug: Leucovorin

Biological: TRK-950

Arm B: TRK-950 + Gemcitabine/Cisplatin

Experimental group

Description:

* Cholangiocarcinoma or Bladder Cancer * TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on days 1 and 8, Cisplatin will be administered by infusion. Then, Gemcitabine will be administered as an IV infusion.

Treatment:

Drug: Gemcitabine

Biological: TRK-950

Drug: Cisplatin

Biological: TRK-950

Biological: TRK-950

Arm C: TRK-950 + Gemcitabine/Carboplatin

Experimental group

Description:

* Ovarian Cancer * TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on days 1 and 8, Gemcitabine will be administered as an intravenous infusion. On day 1, following the administration of TRK-950 and Gemcitabine, Carboplatin will be administered IV.

Treatment:

Drug: Gemcitabine

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: Carboplatin

Arm D: TRK-950 + Ramucirumab/Paclitaxel

Experimental group

Description:

* Gastric Cancer * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Ramucirumab will be administered as an IV infusion. Paclitaxel will be dosed on days 1, 8 and 15, after the Ramucirumab on days 1 and 15 and after the TRK-950 on day 8.

Treatment:

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: Ramucirumab

Drug: Paclitaxel

Arm E: TRK-950 + PD1 inhibitors

Experimental group

Description:

•Solid Tumors E-1: TRK-950 + Nivolumab •TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Nivolumab will be administered as an IV infusion. E-2: TRK-950 + Pembrolizumab •TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on day 1, Pembrolizumab will be administered as an IV infusion.

Treatment:

Biological: TRK-950

Drug: Nivolumab

Biological: TRK-950

Biological: TRK-950

Drug: Pembrolizumab

Arm F: TRK-950 + Imiquimod Cream

Experimental group

Description:

* Palpable subcutaneous malignant lesions * TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. Imiquimod cream is to be applied 5 of 7 days in a row with 2 days rest for a maximum of 2 cycles (total 6 weeks).

Treatment:

Biological: TRK-950

Drug: Imiquimod Cream

Biological: TRK-950

Biological: TRK-950

Arm G: TRK-950 + Bevacizumab

Experimental group

Description:

* Renal Cell Carcinoma * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Bevacizumab will be administered as an IV infusion.

Treatment:

Drug: Bevacizumab

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Arm H: TRK-950 + PD1 inhibitors

Experimental group

Description:

•Melanoma H-1: TRK-950 + Nivolumab •TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. After the administration of TRK-950 on days 1 and 15, Nivolumab will be administered as an IV infusion. H-2: TRK-950 + Pembrolizumab •TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. After the administration of TRK-950 on day 1, Pembrolizumab will be administered as an IV infusion.

Treatment:

Biological: TRK-950

Drug: Nivolumab

Biological: TRK-950

Biological: TRK-950

Drug: Pembrolizumab

Arm J: TRK-950 + FOLFIRI

Experimental group

Description:

* Colorectal Cancer * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On days 1 and 15 Irinotecan will be administered IV. Leucovorin will be infused to match the duration of the irinotecan infusion. 5-FU will be administered as IV bolus, followed by TRK-950 administration. After the TRK-950, 5-FU will be administered by a continuous infusion.

Treatment:

Drug: Irinotecan

Drug: 5-FU

Biological: TRK-950

Biological: TRK-950

Drug: Leucovorin

Biological: TRK-950

Arm K: TRK-950 + Gemcitabine / Carboplatin / Bevacizumab

Experimental group

Description:

* Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer * TRK-950 will be administered IV on days 1, 8 and 15 of a 21-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. Gemcitabine will be administered as an intravenous infusion on days 1 and 8. On day 1, following the administration of Gemcitabine, Carboplatin will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next. After 6 cycles of chemotherapy the patient will be transitioned to maintenance treatment. On Day 1 of each maintenance cycle, Bevacizumab will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease.

Treatment:

Drug: Bevacizumab

Drug: Gemcitabine

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: Carboplatin

Arm O: TRK-950 + PLD

Experimental group

Description:

* Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. PLD will be dosed as IV on Day 1 of each cycle. On days that TRK-950 and PLD are both dosed, PLD will be dosed first.

Treatment:

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: PLD

Arm Q: TRK-950 + Ramucirumab/Paclitaxel

Experimental group

Description:

* Gastric cancer * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On all dosing days, TRK-950 will be administered IV after the relevant combination regimen is dosed. On days 1 and 15, ramucirumab will be administered IV. Paclitaxel will be dosed on days 1, 8 and 15, after ramucirumab on days 1 and 15, before TRK-950 on day 8.

Treatment:

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: Ramucirumab

Drug: Paclitaxel

Arm R: TRK-950 + Bevacizumab

Experimental group

Description:

* Renal cell carcinoma cancer * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. Bevacizumab will be dosed as IV on Day 1 and 15 of each cycle. On days that TRK-950 and Bevacizumab are both dosed, Bevacizumab will be dosed first.

Treatment:

Drug: Bevacizumab

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Arm S: TRK-950 + Carboplatin / PLD/ Bevacizumab

Experimental group

Description:

* Platinum Sensitive epithelial ovarian, primary peritoneal or fallopian tube cancer * Treatment Phase: TRK-950 will be administered IV on days 1 and 15 of a 28-day cycle. Carboplatin will be administered as an intravenous infusion on day 1. On day 1, following the administration of Carboplatin, PLD will be administered as an intravenous infusion. Also on Day 1 of each cycle, Bevacizumab will be administered IV next. On days 1 and 15, TRK-950 will be administered IV after the Bevacizumab infusion. • Maintenance Phase: After 6 cycles of chemotherapy, the patient will be transitioned to maintenance treatment. On Day 1 of each maintenance cycle, Bevacizumab will be administered IV. Following the Bevacizumab administration, TRK-950 will be administered IV. Maintenance treatment will be continued as long as there is no evidence of progressive disease.

Treatment:

Drug: Bevacizumab

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: Carboplatin

Drug: PLD

Arm T: TRK-950 + Paclitaxel

Experimental group

Description:

* Platinum Resistant epithelial ovarian, primary peritoneal or fallopian tube cancer * TRK-950 will be administered IV on days 1, 8, 15, and 22 of a 28-day cycle. On days 1, 8 and 15 of each cycle, Paclitaxel will be dosed on IV

Treatment:

Biological: TRK-950

Biological: TRK-950

Biological: TRK-950

Drug: Paclitaxel