Gemcitabine + Nab-paclitaxel + IM156 for Pancreatic Cancer

Overseen By Shubham Pant, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Biguanides, CYP2D6 substrates

Disqualifiers: Diabetes, Serious infections, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with metastatic pancreatic cancer. Researchers aim to determine if adding a new drug, IM156 (an experimental treatment), to the current standard treatments, gemcitabine and nab-paclitaxel, is safe and can improve outcomes. The trial seeks participants diagnosed with metastatic pancreatic cancer who have not yet received treatment. This study could provide a new option for those seeking innovative cancer care solutions. As a Phase 1 trial, participants will be among the first to receive this new treatment, assisting researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, specifically those that are sensitive CYP2D6 substrates and biguanides like metformin. If you are on these medications, you would need to stop them to participate in the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using IM156 with gemcitabine and nab-paclitaxel is generally safe for people with pancreatic cancer. In a recent study, most patients tolerated this combination well, with only a few experiencing serious side effects, specifically, few serious blood-related problems.

Gemcitabine and nab-paclitaxel are already known to be safe and effective for treating pancreatic cancer, making the addition of IM156 promising. Although the treatment did not significantly improve tumor shrinkage, safety remains a key focus. Patients should consult their doctors to understand what these results might mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Gemcitabine + Nab-paclitaxel + IM156 for pancreatic cancer because IM156 represents a novel approach. Unlike standard chemotherapy options like FOLFIRINOX or gemcitabine with nab-paclitaxel alone, IM156 is being studied for its potential to enhance the effectiveness of these existing drugs. It targets metabolic pathways in cancer cells that are not addressed by current treatments, which could lead to improved outcomes. This innovative combination aims to capitalize on the strengths of traditional chemotherapy while introducing a new mechanism that could suppress tumor growth more effectively.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that combining gemcitabine with nab-paclitaxel helps patients with advanced pancreatic cancer live longer and reduces tumor size more effectively than gemcitabine alone. This combination has improved survival rates. In a recent study, 42% of patients experienced tumor shrinkage with this treatment, and all patients achieved some level of disease control. This trial explores adding a new drug, IM156, to determine if it can further enhance these results by overcoming treatment resistance. ^{1 3 4 5 6}

Who Is on the Research Team?

Shubham Pant, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic cancer who haven't had treatment for metastatic disease. They must understand the study and agree to sign a consent form, have measurable disease, possibly be HIV-positive but with undetectable viral load, not be on certain medications or have serious health issues that could affect safety or compliance.

Inclusion Criteria

Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

I finished any previous cancer treatments at least 6 months ago.

I have not received any treatment for my cancer since it spread.

Exclusion Criteria

Patients with uncontrolled underlying medical conditions

Pregnant or breastfeeding women are excluded

Patients with a history of alcohol or drug abuse within 12 weeks prior to screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Identify the recommended phase 2 dose (RP2D) of IM156 in combination with gemcitabine and nab-paclitaxel

8-12 weeks

Dose Expansion

Evaluate IM156 at the RP2D with gemcitabine and nab-paclitaxel

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• IM156
• Nab paclitaxel

Trial Overview The study tests if IM156 added to gemcitabine and nab-paclitaxel is safe and improves treatment outcomes in patients with advanced pancreatic cancer. It's an early-phase trial to assess this combination's tolerability and potential effectiveness.

How Is the Trial Designed?

Group I: Dose Escalation Phase followed by a Dose Expansion Phase Experimental Treatment 3 Interventions

In the Dose Escalation Phase of the study, we will identify the RPD2 of IM156. Subsequently, we will evaluate IM156 at the RP2D (established in the Dose Expansion Phase) and gemcitabine + nab-paclitaxel in the Dose Expansion Phase.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

In a study of 27 patients with unresectable pancreatic cancer, nab paclitaxel plus gemcitabine was found to be effective and well-tolerated in elderly patients aged 75 and older, showing similar disease control rates and overall survival compared to younger patients.

Despite a lower relative dose intensity of the drugs in the elderly group, the safety profile was comparable, with neutropenia being the most common severe adverse event, indicating that this treatment regimen can be safely administered to older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. Ishimoto, U., Kinoshita, A., Hirose, Y., et al.[2022]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a study involving 866 patients with resected pancreatic ductal adenocarcinoma, the combination of nab-paclitaxel and gemcitabine showed a significant improvement in overall survival (OS) compared to gemcitabine alone, with a median OS of 41.8 months versus 37.7 months, respectively.

Although the primary endpoint of disease-free survival (DFS) was not significantly improved with nab-paclitaxel + gemcitabine, the treatment was associated with a higher incidence of grade ≥ 3 adverse events (86% vs. 68% for gemcitabine), indicating a need for careful consideration of safety alongside efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero, MA., Pelzer, U., O'Reilly, EM., et al.[2023]

In a phase II trial involving 61 patients with borderline resectable pancreatic cancer, the neoadjuvant therapy of nab-paclitaxel plus gemcitabine resulted in a median overall survival of 25.2 months and a median recurrence-free survival of 12.3 months, indicating promising efficacy.

The treatment had a high resection rate of 73.8% and an R0 resection rate of 63.9%, but it also presented significant safety concerns, with 73.8% of patients experiencing grade 3/4 adverse events, highlighting the need for careful patient selection, especially for those with prior lung issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). Okada, KI., Kimura, K., Yamashita, YI., et al.[2023]

In a study of 12 patients with elevated bilirubin levels, the combination of gemcitabine (GEM) and nab-paclitaxel (NabP) showed a median overall survival of 13.9 months, indicating improved efficacy compared to previous findings with GEM alone.

The treatment was found to be safe, with no admissions related to toxicity, and a disease control rate of 58%, suggesting that GEM-NabP can be effectively administered to patients who were previously excluded from studies due to hyperbilirubinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia. Rogers, JE., Mizrahi, JD., Shroff, RT., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05497778

A Phase 1b Study of Gemcitabine and Nab-paclitaxel in ... Primary Safety Objective: To evaluate the safety and tolerability of IM156 with Gem+NP in patients with metastatic PDAC. Exploratory Efficacy Objective:.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36181099/

The effectiveness of nab-paclitaxel plus gemcitabine and ... FOLFIRINOX and nab-paclitaxel plus gemcitabine demonstrated a survival benefit compared to gemcitabine alone. Both protocols are now considered ...

3. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-1-2023-05e4e

Gemcitabine + Nab-paclitaxel + IM156 for Pancreatic Cancer Research shows that combining Gemcitabine and Nab-paclitaxel improves survival rates and tumor response in patients with advanced pancreatic cancer compared to ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00481-8/fulltext

263P A phase Ib dose-escalation trial of gemcitabine and ... Among response-evaluable patients treated at RP2D, the objective response rate (ORR) was 42% (5 partial responses), and the disease control rate (DCR) was 100%.

5. immunomet.com immunomet.com/immunomet-therapeutics-announces-first-patient-dosed-in-a-phase-1b-trial-of-im156-in-pancreatic-cancer/

ImmunoMet Therapeutics Announces First Patient Dosed ... This clinical trial evaluates the potential of IM156 in combination with gemcitabine and nab-paclitaxel to address resistance and improve patient outcomes. The ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32957885/

Clinical Outcomes and Safety of Patients Treated with NAb ... Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.