TAK-676 + Pembrolizumab for Metastatic Cancer (iintune-1 Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Takeda
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called dazostinag, alone and with another drug called pembrolizumab, to treat people with advanced solid tumors. It focuses on patients with specific types of head and neck cancer and colorectal cancer who have few other treatment options. The goal is to find a safe dose and see if the combination can help the immune system fight the cancer more effectively.
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications like systemic corticosteroids or immunosuppressive therapy within 7 days of starting the study drugs, and you should avoid medications that inhibit OATP1B1 and OATP1B3 within 14 days of starting. It's best to discuss your specific medications with the trial team.
Is the drug Pembrolizumab, used in the trial TAK-676 + Pembrolizumab for Metastatic Cancer, a promising treatment?Yes, Pembrolizumab is a promising drug. It has shown positive results in treating various cancers, including non-small cell lung cancer and melanoma. It works by helping the immune system fight cancer cells more effectively.145910
What safety data is available for the treatment of TAK-676 and Pembrolizumab for metastatic cancer?The safety data for Pembrolizumab, a PD-1 inhibitor, shows it is generally well tolerated with a favorable safety profile. Common adverse events include fatigue, rash, itching, and diarrhea, while less frequent immune-related adverse events include hypothyroidism, colitis, hepatitis, and pneumonitis. In various studies, Pembrolizumab has been used in different cancer types, including metastatic melanoma and non-small cell lung cancer, with manageable toxicities. However, specific safety data for the combination of TAK-676 and Pembrolizumab is not detailed in the provided research.126910
What data supports the idea that TAK-676 + Pembrolizumab for Metastatic Cancer is an effective treatment?The available research shows that Pembrolizumab, when used with other drugs like pemetrexed and platinum, has improved survival rates and slowed disease progression in patients with metastatic non-small-cell lung cancer. Although the specific combination of TAK-676 and Pembrolizumab for metastatic cancer isn't directly covered, Pembrolizumab alone has shown positive results in various studies for similar conditions, suggesting its potential effectiveness.13789
Eligibility Criteria
Adults with advanced or metastatic solid tumors who haven't responded to standard treatments, or can't tolerate them, may join this trial. They should be in good physical condition (ECOG 0-1), have not received certain vaccines recently, and must not have active hepatitis or heart issues. Smokers and those with specific lung conditions cannot participate.Inclusion Criteria
CRC (Part 3): Third-line or later MSI-H/dMMR CRC (Part 3A): histologically confirmed recurrent locally advanced or metastatic MSI-H/dMMR CRC with disease progression on or following therapy with anti-PD-1 or PD-L1 antibody and at least one line of combination chemotherapy, Third-line MSS/pMMR CRC (Part 3B): histologically confirmed recurrent locally advanced or metastatic MSS/pMMR CRC with disease progression on or following therapy with 2 different lines of combination chemotherapy, MSI/MMR status confirmed by a clinically-approved IHC and/or PCR assay, treated with 2 prior lines of therapy in the recurrent locally advanced or metastatic setting
I have advanced cancer with no standard treatment options left or cannot tolerate them.
I can carry out all my daily activities without help.
My cancer is advanced or has spread, and standard treatments haven't worked or can't be used.
My cancer did not respond to previous immunotherapy treatments.
My advanced cancer has no standard treatment options left, or I can't tolerate them.
I am fully active or can carry out light work.
My tumor has not been treated with anti-PD-1 or anti-PD-L1 therapy.
Exclusion Criteria
I cannot take pembrolizumab due to adverse reactions or medical reasons.
My brain metastasis has been stable for over 6 weeks, and I'm not on corticosteroids.
I do not have severe lung problems or uncontrolled fluid in my lungs or abdomen.
I have experienced moderate to severe low blood pressure.
I cannot tolerate or am allergic to platinum-based chemotherapy and 5-FU.
I have ongoing, active hepatitis.
I currently have a serious infection or a high fever due to cancer.
I have refused all standard treatments available.
I am not taking drugs that affect liver transport proteins.
I have received a stem cell or organ transplant.
I am not on any cancer treatment except hormone therapy for breast cancer.
Treatment Details
The study is testing TAK-676 alone and combined with Pembrolizumab to find the highest dose patients can take without severe side effects. It includes a phase where doses increase (dose escalation) followed by a phase that tests the chosen dose more broadly (dose expansion). Some will also receive chemotherapy drugs like Platinum and 5-fluorouracil.
8Treatment groups
Experimental Treatment
Group I: Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRCExperimental Treatment2 Interventions
Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite stable/mismatch repair proficient (MSS/pMMR) CRC at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. along with pembrolizumab 200 mg infusion, IV, Q3W.
Group II: Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRCExperimental Treatment2 Interventions
Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite instability-high /mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.
Group III: Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + ChemotherapyExperimental Treatment4 Interventions
Dazostinag 5.0 mg, infusion, IV, will be administered in participants with SCCHN at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. Pembrolizumab infusion, IV will be administered at 200 mg Q3W. Platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 milligrams per milli Liters per minute (mg/mL/minute) \[AUC 5\]) or cisplatin (100 milligrams per square meter \[mg/m\^2\] Day 1 of each treatment cycle), and 5-fluorouracil (\[5-FU\]; 1000 mg/m\^2 per day for 4 consecutive days) Q3W for up to 6 cycles.
Group IV: Part 2A (SCCHN CPS ≥ 1 Dose Expansion and Optimization Phase): Dazostinag + PembrolizumabExperimental Treatment2 Interventions
Dazostinag 5.0 mg, infusion, IV, will be administered in participants with squamous cell carcinoma of head and neck (SCCHN) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W. Dose optimization may be performed in this phase.
Group V: Part 1B (Combination Dose Escalation Phase): Dazostinag + PembrolizumabExperimental Treatment2 Interventions
Dazostinag escalating doses (0.2 mg and above) in combination with pembrolizumab 200 mg, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycle. Pembrolizumab 200 mg will be administered 1 hour prior to Dazostinag once every 3 weeks (Q3W). The dosing will be initiated when at least two dose levels (DLs) of Part 1A have been evaluated.
Group VI: Part 1 (Monotherapy Dose Escalation Phase): Dazostinag Safety Lead-in + Dazostinag SA [Part 1A]Experimental Treatment1 Intervention
Safety Lead-in: Dazostinag 0.1 mg, infusion, intravenously (IV), once weekly, on Days 1, 8 and 15 in 21-day treatment cycles.
Dazostinag SA Dose Escalation (Part 1A): Dazostinag single agent (SA), infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above). The dosing will be initiated in the Dazostinag SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in.
Group VII: Arm B: Japan Safety Lead-in Dazostinag Transitioned to PembrolizumabExperimental Treatment2 Interventions
Dazostinag 5.0 mg, infusion, IV, as an SA once on Day 1 in Cycle 0 (cycle length=7 days) in Japanese participants with advanced or metastatic solid tumors based on confirmation of tolerability in Arm A. Following Cycle 0 (7 days), participants will be transitioned to the same dose level of dazostinag on Days 1, 8, and 15 of each 21-day cycle in combination with pembrolizumab administered Q3W, IV, on Day 1 in each 21-day cycle.
Additional dose levels of dazostinag (such as ≥ 7.0 mg) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead-in.
Group VIII: Arm A: Japan Safety Lead-in Dazostinag + PembrolizumabExperimental Treatment2 Interventions
Dazostinag 5.0 mg, infusion, IV, in Japanese participants with advanced or metastatic solid tumors on Days 1, 8, and 15 in each 21-day cycle in combination with pembrolizumab 200 mg administered Q3W, IV, on Day 1 in each 21-day cycle.
Additional dose levels of Dazostinag (such as 14.0 mg) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead-in.
Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇪🇺 Approved in European Union as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇬🇧 Approved in United Kingdom as KEYTRUDA for:
- Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
Find a clinic near you
Research locations nearbySelect from list below to view details:
Sarah Cannon Research Institute (SCRI)Nashville, TN
Sarah Cannon Research Institute- HealthOne, DenverDenver, CO
University of Pittsburgh Medical Center - Hillman Cancer CenterPittsburgh, PA
SCRI - HealthOne DenverDenver, CO
More Trial Locations
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Who is running the clinical trial?
TakedaLead Sponsor
References
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab. [2017]Currently, limited data exist on the safety of pembrolizumab in patients with metastatic melanoma who have developed severe immune-related adverse events following treatment with ipilimumab. We report a 45-year-old male patient with BRAF-mutant metastatic melanoma who discontinued treatment with ipilimumab due to treatment-related grade 3 colitis and was subsequently treated with the anti-programmed cell death 1 protein (PD-1) antibody pembrolizumab. He has been on treatment with pembrolizumab for more than 20 months with no major toxicities and has achieved an objective partial response, which is ongoing.
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).
Pembrolizumab in the management of metastatic melanoma. [2020]Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that plays a major role in the treatment of advanced melanoma. Through blockade of PD-1, it leads to an increase in effector T-cell activity in the tumor microenvironment. Clinical trial outcomes for pembrolizumab in addition to pharmacokinetics, pharmacodynamics and safety of the compound are discussed in this article. Phase I trials have demonstrated safety and efficacy of pembrolizumab in advanced, pretreated melanoma patients. When compared with chemotherapy in a Phase II trial of ipilimumab-refractory patients, those treated with pembrolizumab showed superior progression-free survival. In addition, in the pivotal Phase III trial pembrolizumab improved overall survival compared with ipilimumab in patients naive to immune checkpoint inhibition. Pembrolizumab is well tolerated and has a favorable safety profile. Common adverse events are fatigue, rash, itching and diarrhea. Less frequent immune-related adverse events include hypothyroidism, colitis, hepatitis and pneumonitis.
Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. [2021]In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680).
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. [2022]Parts 4 and 5 of the phase 1/2 KEYNOTE-022 study investigated the maximum tolerated dose (MTD), safety, and efficacy of pembrolizumab plus trametinib in solid tumours and BRAF wild-type melanoma.