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

NCT03872947 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 950P1V02
• Study Type: interventional
• Target: 138
• Locations: 2 countries
• Sites: 14

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (12)

• Frequency of patients experiencing treatment emergent adverse events as assessed by CTCAE v5.0

  through study completion, an average of 1 year

• Frequency of patients experiencing adverse events of special interest (AESIs)

  through study completion, an average of 1 year

• Blood pressure

  mmHg

  through study completion, an average of 1 year

• Heart rate

  bpm

  through study completion, an average of 1 year

• Respiratory rate

  bpm

  through study completion, an average of 1 year

• Temperature

  °F or °C

  through study completion, an average of 1 year

• Weight

  lbs/kg

  through study completion, an average of 1 year

• Height

  inches/cm

  through study completion, an average of 1 year

• Performance status using Karnofsky performance status criteria

  through study completion, an average of 1 year

• QTc interval determined from 12-lead Electrocardiogram

  msec

  through study completion, an average of 1 year

• QRS interval determined from 12-lead Electrocardiogram

  msec

  through study completion, an average of 1 year

• Frequency of patients with laboratory abnormalities (Complete Blood Count, Coagulation, Urinalysis and Serum Chemistry)

  through study completion, an average of 1 year

Secondary Outcomes (10)

• Overall response rate (ORR)

  through study completion, an average of 1 year

• Disease Control Rate (DCR)

  through study completion, an average of 1 year

• Serum concentration of TRK-950

  through study completion, an average of 1 year

• Plasma concentration of Gemcitabine for the first six patients in Arm K

  At the beginning of Cycle 1 and Cycle 4 (each cycle is 21 days)

• Plasma concentration of Carboplatin for the first six patients in Arm K

  At the beginning of Cycle 1 and Cycle 4 (each cycle is 21 days)

Study Arms (15)

Arm A: TRK-950 + FOLFIRI

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU

Arm B: TRK-950 + Gemcitabine/Cisplatin

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Gemcitabine; Drug: Cisplatin

Arm C: TRK-950 + Gemcitabine/Carboplatin

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Gemcitabine; Drug: Carboplatin

Arm D: TRK-950 + Ramucirumab/Paclitaxel

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Ramucirumab; Drug: Paclitaxel

Arm E: TRK-950 + PD1 inhibitors

EXPERIMENTAL

•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.

Biological: TRK-950; Drug: Nivolumab; Drug: Pembrolizumab

Arm F: TRK-950 + Imiquimod Cream

EXPERIMENTAL

* 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).

Biological: TRK-950; Drug: Imiquimod Cream

Arm G: TRK-950 + Bevacizumab

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Bevacizumab

Arm H: TRK-950 + PD1 inhibitors

EXPERIMENTAL

•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.

Biological: TRK-950; Drug: Nivolumab; Drug: Pembrolizumab

Arm J: TRK-950 + FOLFIRI

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU

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

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Gemcitabine; Drug: Carboplatin; Drug: Bevacizumab

Arm O: TRK-950 + PLD

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: PLD

Arm Q: TRK-950 + Ramucirumab/Paclitaxel

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Ramucirumab; Drug: Paclitaxel

Arm R: TRK-950 + Bevacizumab

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Bevacizumab

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

EXPERIMENTAL

* 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.

Biological: TRK-950; Drug: Carboplatin; Drug: Bevacizumab; Drug: PLD

Arm T: TRK-950 + Paclitaxel

EXPERIMENTAL

* 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

Biological: TRK-950; Drug: Paclitaxel

Interventions

TRK-950 BIOLOGICAL

10 mg/kg administered intravenously over 60 minutes (weekly)

Arm A: TRK-950 + FOLFIRI; Arm B: TRK-950 + Gemcitabine/Cisplatin; Arm C: TRK-950 + Gemcitabine/Carboplatin; Arm D: TRK-950 + Ramucirumab/Paclitaxel; Arm E: TRK-950 + PD1 inhibitors; Arm F: TRK-950 + Imiquimod Cream; Arm G: TRK-950 + Bevacizumab; Arm H: TRK-950 + PD1 inhibitors; Arm J: TRK-950 + FOLFIRI; Arm T: TRK-950 + Paclitaxel

Irinotecan DRUG

Intravenously over 30 - 90 minutes

Arm A: TRK-950 + FOLFIRI; Arm J: TRK-950 + FOLFIRI

Leucovorin DRUG

Intravenously over 30 - 90 minutes

Arm A: TRK-950 + FOLFIRI; Arm J: TRK-950 + FOLFIRI

5-FU DRUG

Intravenously bolus and intravenously for two days

Arm A: TRK-950 + FOLFIRI; Arm J: TRK-950 + FOLFIRI

Gemcitabine DRUG

Intravenously over 30 minutes

Arm B: TRK-950 + Gemcitabine/Cisplatin; Arm C: TRK-950 + Gemcitabine/Carboplatin; Arm K: TRK-950 + Gemcitabine / Carboplatin / Bevacizumab

Cisplatin DRUG

Intravenously over 60 minutes

Arm B: TRK-950 + Gemcitabine/Cisplatin

Carboplatin DRUG

Intravenously per package insert

Arm C: TRK-950 + Gemcitabine/Carboplatin; Arm K: TRK-950 + Gemcitabine / Carboplatin / Bevacizumab; Arm S: TRK-950 + Carboplatin / PLD/ Bevacizumab

Ramucirumab DRUG

Intravenously over 60 minutes

Arm D: TRK-950 + Ramucirumab/Paclitaxel; Arm Q: TRK-950 + Ramucirumab/Paclitaxel

Paclitaxel DRUG

Intravenously

Arm D: TRK-950 + Ramucirumab/Paclitaxel; Arm Q: TRK-950 + Ramucirumab/Paclitaxel; Arm T: TRK-950 + Paclitaxel

Nivolumab DRUG

Intravenously over 30 minutes

Arm E: TRK-950 + PD1 inhibitors; Arm H: TRK-950 + PD1 inhibitors

Pembrolizumab DRUG

Intravenously over 30 minutes

Arm E: TRK-950 + PD1 inhibitors; Arm H: TRK-950 + PD1 inhibitors

Imiquimod Cream DRUG

Topically

Arm F: TRK-950 + Imiquimod Cream

Bevacizumab DRUG

Intravenously over 90 minutes for the first dose, over 60 for the second dose and over 30 minutes for all subsequent doses

Arm G: TRK-950 + Bevacizumab; Arm K: TRK-950 + Gemcitabine / Carboplatin / Bevacizumab; Arm R: TRK-950 + Bevacizumab; Arm S: TRK-950 + Carboplatin / PLD/ Bevacizumab

PLD DRUG

Intravenously over 60 minutes

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Toray Industries, Inc: lead

Study Sites (14)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

AOA-HOPE

Tucson, Arizona, 85711, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

HOAG Memorial Hospital Presbyterian

Newport, California, 92663, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute and Research Center)

Eugene, Oregon, 97401, United States

Location

Northwest Cancer Specialists

Portland, Oregon, 97227, United States

Location

Texas Oncology, P.A. Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology - Downtown Fort Worth Cancer Center

Fort Worth, Texas, 76104, United States

Location

Virginia Cancer Specialists, PC

Leesburg, Virginia, 20176, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Related Publications (1)

• Okano F, Saito T, Minamida Y, Kobayashi S, Ido T, Miyauchi Y, Wasai U, Akazawa D, Kume M, Ishibashi M, Jiang K, Aicher A, Heeschen C, Yonehara T. Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950. Cancer Res Commun. 2023 Apr 18;3(4):640-658. doi: 10.1158/2767-9764.CRC-22-0310. eCollection 2023 Apr.

  PMID: 37082579 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Cholangiocarcinoma; Urinary Bladder Neoplasms; Ovarian Neoplasms; Stomach Neoplasms; Carcinoma, Renal Cell; Melanoma; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms

Interventions

Irinotecan; Leucovorin; Fluorouracil; Gemcitabine; Cisplatin; Carboplatin; Ramucirumab; Paclitaxel; Nivolumab; pembrolizumab; Bevacizumab; 1-dodecylpyridoxal

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Stomach Diseases; Kidney Neoplasms; Kidney Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2019
• First Posted: March 13, 2019
• Study Start: April 26, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); FR (1)