AK112 +/− AK117 for Colorectal Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Akeso

Must not be taking: Immunotherapy

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is a Phase II study. The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of AK112 with or without AK117 in participants with metastatic colorectal cancer who are not suitable for surgery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination AK112 +/− AK117 for colorectal cancer?

Research shows that drugs like 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and irinotecan, which are part of the treatment, have improved survival rates in colorectal cancer patients. Additionally, capecitabine, a drug that turns into 5-FU in the body, is effective and well-tolerated, especially when combined with other drugs like oxaliplatin and irinotecan.

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Is the treatment AK112 +/− AK117 for colorectal cancer generally safe in humans?

The safety of treatments like capecitabine (Xeloda) and 5-fluorouracil (5-FU), often used in colorectal cancer, has been well-studied. Capecitabine is known for its favorable safety profile compared to 5-FU, and both are commonly used in combination with other drugs like oxaliplatin and irinotecan, showing good tolerability in patients.

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What makes the AK112 +/− AK117 drug for colorectal cancer unique?

The AK112 +/− AK117 drug for colorectal cancer is unique because it combines traditional chemotherapy agents like 5-FU, capecitabine, and oxaliplatin with targeted therapies such as bevacizumab, potentially enhancing effectiveness by attacking cancer cells in multiple ways. This combination aims to improve survival rates and manage side effects better than standard treatments.

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Eligibility Criteria

This trial is for adults with metastatic colorectal cancer that can't be removed by surgery. Participants must have a specific type of tumor, not had systemic therapy for metastasis, and should have received 2-4 prior lines of anticancer therapy. They need to be relatively active (good performance status) and have tumors measurable by certain medical criteria.

Inclusion Criteria

My diagnosis is colorectal cancer confirmed by tissue analysis.

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer returned or spread 12 months after my last cancer treatment.

Exclusion Criteria

Pregnancy or lactation

My cancer is MSI-H or has dMMR.

History of autoimmune disease

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Regimen Selection

Participants receive AK112 with or without AK117 in combination with XELOX or FOLFOXIRI to determine the optimal chemotherapy regimen

3-6 weeks

Biweekly visits for chemotherapy administration

Maintenance Treatment

Participants receive maintenance therapy with capecitabine plus AK112 plus AK117 or 5-FU/LV plus AK112 plus AK117 until disease progression or unacceptable toxicity

Until disease progression or unacceptable toxicity

Biweekly visits for maintenance therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 2 years

Participant Groups

The study tests AK112 alone or combined with AK117 in treating metastatic colorectal cancer. It's a Phase II trial focusing on how well these treatments work, their safety, and how the body processes them. Standard chemotherapy drugs may also be used.

Group I: Part 2 cohort 2(AK112+AK117) Experimental Treatment 2 Interventions

Subjects receive AK117 and AK112 until disease progression or unacceptable toxicity AK112 and AK117 ( until disease progression, unacceptable toxicity or patient's refusal)

Group II: Part 2 cohort 1(AK112) Experimental Treatment 1 Intervention

Subjects receive AK112 until disease progression or unacceptable toxicity AK112 (until disease progression, unacceptable toxicity or patient's refusal)

Group III: Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6) Experimental Treatment 4 Interventions

AK112 (Dose2) +mFOLFOX6 ( Oxaliplatin 85 mg/sqm IV day 1, Leucovorin 400 mg/sqm IV day 1, 5-fluorouracil(5-FU) 2400 mg/sqm 46-48 hours continuous infusion, starting on day 1) If no progression occurs during AK112 plus mFOLFOX6, patients will receive maintenance 5- FU/LV plus AK112 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

Group IV: Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6) Experimental Treatment 4 Interventions

AK112 (Dose1) +mFOLFOX6 ( Oxaliplatin 85 mg/sqm IV day 1, Leucovorin 400 mg/sqm IV day 1, 5-fluorouracil(5-FU) 2400 mg/sqm 46-48 hours continuous infusion, starting on day 1). If no progression occurs during AK112 plus mFOLFOX6, patients will receive maintenance 5- FU/LV plus AK112 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

Group V: Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy) Experimental Treatment 7 Interventions

AK112(Dose2)+AK117(Dose1)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Group VI: Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy) Experimental Treatment 7 Interventions

AK112(Dose2) + AK117(Dose2)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Group VII: Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy) Experimental Treatment 6 Interventions

AK112 (Dose2)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage). AK112 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage).

Group VIII: Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy) Experimental Treatment 7 Interventions

AK112 (Dose1) +AK117 (Dose1) +Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Group IX: Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy) Experimental Treatment 6 Interventions

AK112 (Dose1) +Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Group X: Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI) Experimental Treatment 6 Interventions

AK112+AK117+FOLFOXIRI AK112 and AK117 and FOLFOXIRI(Irinotecan 150-165 mg/sqm iv day 1, Oxaliplatin 85 mg/sqm iv day 1, Leucovorin(LV) 400 mg/sqm iv day 1, 5-fluorouracil(5-FU) 2400-2800 mg/sqm 46-48 hours continuous infusion, starting on day 1) If no progression occurs during AK112 plus AK117 plus FOLFOXIRI, patients will receive maintenance 5-FU/LV plus AK112 plus AK117 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 plus AK117 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

Group XI: Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX) Experimental Treatment 4 Interventions

AK112+AK117+XELOX AK112 and AK117 and XELOX(Oxaliplatin 130 mg/sqm iv day 1, Capecitabine via oral, the total daily dose was 2000mg/sqm, day1-14) If no progression occurs during AK112 plus AK117 plus XELOX, patients will receive maintenance capecitabine plus AK112 plus AK117 at the same dose used at the last cycle of the induction treatment. Capecitabine plus AK112 plus AK117 will be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal.

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

🇺🇸 Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

🇪🇺 Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

🇨🇦 Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

🇯🇵 Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Valkyrie Clinical Trials Los Angeles, CA

Who Is Running the Clinical Trial?

Akeso Lead Sponsor

Summit Therapeutics Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Oral capecitabine: bridging the Atlantic divide in colon cancer treatment. [2018] 5-Fluorouracil (5-FU) plus leucovorin (LV) has been the mainstay of treatment for colorectal cancer (CRC), with infused schedules more widely adopted in Europe and bolus schedules preferred in North America. However, the effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV on both sides of the Atlantic. Capecitabine generates 5-FU preferentially in tumor and is a well-established, first-line treatment for metastatic CRC. In this setting, capecitabine achieves a superior response rate, at least equivalent time to disease progression (TTP) and overall survival, and favorable safety compared with bolus 5-FU/LV. The benefits of capecitabine have been transfered into the adjuvant setting. Recent data from a large, international, randomized trial (Xeloda Adjuvant Chemotherapy Trial [X-ACT]) confirm that capecitabine (Xeloda, Roche Laboratories, Nutley, NJ) achieves favorable safety versus 5-FU/LV (Mayo Clinic regimen) and is at least as effective as IV 5-FU/LV in the adjuvant treatment of patients with resected stage III colon cancer. Capecitabine is also an effective and well-tolerated combination partner for oxaliplatin (XELOX) and irinotecan (XELIRI), achieving high efficacy with a good safety profile. An extensive phase III clinical trial program is further establishing the potential of the simplified capecitabine combinations to improve outcomes and unify treatment practices in the metastatic and adjuvant settings. New combinations with novel agents such as capecitabine/oxaliplatin plus erlotinib or bevacizumab are currently under investigation. Capecitabine has also shown promising activity and good tolerability in combination with radiotherapy in rectal cancer.

2. England pubmed.ncbi.nlm.nih.gov

Rapid evolution in colorectal cancer: therapy now and over the next five years. [2007] A large number of patients with colorectal cancer have relatively early disease, and thus, adjuvant therapy has the potential to save lives. In stage III patients, there has been a steady improvement in 3-year disease-free survival with the use of 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine (Xeloda); Hoffmann-La Roche Inc., Nutley, NJ, http://www.rocheusa.com) regimens. A median survival longer than 20 months was observed in patients with metastatic disease when treated with combination chemotherapy containing oxaliplatin (Eloxatin); Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) or irinotecan (Camptosar); Pfizer Pharmaceuticals, New York, http://www.pfizer.com). This has led to 5-FU/LV/oxaliplatin becoming standard therapy, along with 5-FU/LV/irinotecan. New data confirm the beneficial effect on disease-free survival of adding oxaliplatin to adjuvant colorectal cancer regimens based on 5-FU. These regimens show an effect when given in bolus as well as in infusional schedules. Interest in future adjuvant regimens focuses on the potential additional benefit of molecularly targeted agents, such as bevacizumab (Avastin); Genentech, Inc., South San Francisco, CA, http://www.gene.com), and on the ability of applied genomics to distinguish between high- and low-risk populations.

3. United States pubmed.ncbi.nlm.nih.gov

FOLFOX alternated with FOLFIRI as first-line chemotherapy for metastatic colorectal cancer. [2022] 5-fluorouracil (5-FU), irinotecan, and oxaliplatin are the most active drugs in advanced colorectal cancer (CRC), and survival is improved with patient exposure to all of them. The efficacy and safety of an alternating schedule of continuous-infusion 5-FU with leucovorin (LV) plus oxaliplatin (ie, FOLFOX regimen) or irinotecan (ie, FOLFIRI regimen) was assessed in the first-line setting.

4. United States pubmed.ncbi.nlm.nih.gov

Oxaliplatin with 5-FU or as a single agent in advanced/metastatic colorectal cancer. [2018] No adequate second- or third-line therapy is available in the United States for patients with metastatic colorectal cancer and disease progression following treatment with fluorouracil (5-FU)-based therapy and an irinotecan (CPT-11, Camptosar)-containing regimen, or a combination of the two. Oxaliplatin (Eloxatin), a new platinum analog, has demonstrated high activity in the treatment of colorectal cancer, especially when combined with 5-FU and leucovorin. The combination of oxaliplatin and 5-FU/leucovorin has been approved in Europe for the first- and second-line treatment of colorectal cancer. This compassionate-use study was initiated because of the unavailability of the agent in the United States and inadequate US safety data. The following review summarizes data from this ongoing study, the primary focus of which is to provide oxaliplatin for compassionate use until it receives US Food and Drug Administration approval and becomes available commercially.

5. United States pubmed.ncbi.nlm.nih.gov

Adjuvant therapy of colon cancer. [2019] The primary curative therapy of colorectal cancer is surgical resection. However, within the last 15 years, prospectively randomized appropriately powered clinical trials have convincingly demonstrated that adjunctive postoperative adjuvant chemotherapy is of benefit to all patients with node-positive disease (stage III) and arguably to high-risk node-negative (stage II) cases. In the United States, the clinical trials encompassing greater than 5,000 cases have demonstrated that fluorouracil (5-FU)/leucovorin used in a variety of doses and schedules improves disease-free and overall survival in resected node-positive (stage III) colorectal cancer. The postoperative use of 5-FU/leucovorin for approximately 6 months represents standard of care for such patients. Current clinical trials are evaluating the role of nonfluorinated pyrimidine chemotherapeutic agents in adjuvant chemotherapy for resected large bowel cancer. 5-FU/leucovorin combined with irinotecan (CPT-11) versus 5-FU/leucovorin are being tested in a national intergroup clinical trial. Another trial is evaluating 5-FU/leucovorin plus oxaliplatin versus 5-FU/leucovorin alone. These clinical trials will be important in defining the appropriate standard of care for patients with resected colorectal cancer, since recent studies in advanced colorectal cancer in the United States and in Western Europe have demonstrated that combinations of 5-FU/leucovorin and CPT-11 or 5-FU/ leucovorin and oxaliplatin are superior to 5-FU/leucovorin alone.

6. United States pubmed.ncbi.nlm.nih.gov

Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial: overview of efficacy, safety, and cost-effectiveness. [2022] The X-ACT (Xeloda in Adjuvant Colon Cancer Therapy) trial compared the efficacy and safety of the oral fluoropyrimidine capecitabine with bolus 5-fluorouracil (5-FU)/leucovorin (LV; Mayo Clinic regimen) as adjuvant therapy for stage III colon cancer. A total of 1987 patients were enrolled at 164 centers worldwide. Disease-free survival (primary study endpoint) in the capecitabine arm was at least equivalent to that in the 5-FU/LV arm; the upper limit of the hazard ratio was significantly (P

7. United States pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022] To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.

8. Germany pubmed.ncbi.nlm.nih.gov

S-1 and irinotecan with or without bevacizumab versus 5-fluorouracil and leucovorin plus oxaliplatin with or without bevacizumab in metastatic colorectal cancer: a pooled analysis of four phase II studies. [2018] S-1, a novel oral prodrug of 5-fluorouracil (5-FU), and irinotecan with or without bevacizumab is known to be effective in metastatic colorectal cancer (mCRC). However, it is not clear whether S-1 and irinotecan confers benefits compared to 5-FU and leucovorin plus oxaliplatin (FOLFOX) in patients with mCRC. Our aim was to compare the efficacy and safety of these regimens.

9. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study. [2020] A phase I-II multicenter trial was conducted to define the maximal tolerated dose and describe the activity of an OCFL combination using oxaliplatin (OHP), irinotecan (CPT-11) and 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (CRC).

10. United States pubmed.ncbi.nlm.nih.gov

Role of oral chemotherapy in colorectal cancer. [2015] Despite the long clinical history of 5-FU in gastrointestinal cancer, the development of oral agents has been a productive endeavor, and oral fluoropyrimidine agents are likely to play an important role in the management of colorectal cancer. Results of recent trials in advanced/metastatic colorectal cancer have shown equivalence of response rates, time to disease progression, and median survival and reduced rates of neutropenia and stomatitis with oral capecitabine (Xeloda) or UFT/leucovorin compared with standard fluorouracil (5-FU)/leucovorin regimens. Evaluation of these oral agents in adjuvant therapy, in combination chemotherapy, and in combination with radiation therapy is ongoing.

11. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer metastasis: the role of chemotherapy. [2019] 5-Fluorouracil (5-FU) has been the main chemotherapeutic agent for the treatment of colorectal cancer for four decades with modest efficacy. Modulation of 5-FU by leucovorin or continuous infusion improves the response rate, but overall survival duration remains approximately 12 months. Many oral fluoropyrimidines have been studied, including capecitabine, UFT, S-1, and Eniluracil. Capecitabine has demonstrated equivalent efficacy with 5-FU and has been approved as first line treatment. The combinations of capecitabine with CPT-11 or oxaliplatin are being developed. CPT-11 demonstrated non-crossover resistance with 5-FU and was proven to be effective treatment for patients who received prior 5-FU. CPT-11 in combination with 5-FU has demonstrated improved response rate and overall survival duration over 5-FU or CPT-11. Oxaliplatin plus 5-FU has offered another effective treatment option for colorectal cancer. Both 5-FU plus leucovorin in combination with CPT-11 or oxaliplatin are widely used first-line chemotherapies for advanced colorectal cancer. Optimal combinations and sequences of treatment are being studied, since several effective regimens have become available.

12. United States pubmed.ncbi.nlm.nih.gov

Randomized multicenter phase II study comparing a combination of fluorouracil and folinic acid and alternating irinotecan and oxaliplatin with oxaliplatin and irinotecan in fluorouracil-pretreated metastatic colorectal cancer patients. [2018] To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination.

13. United States pubmed.ncbi.nlm.nih.gov

Current approaches to first-line treatment of advanced colorectal cancer. [2019] The multiplicity of chemotherapy regimens currently available to treat colorectal cancer in the first-line setting precludes the identification of a single standard regimen for front-line therapy. The previous standard, 5-fluorouracil (5-FU), formerly the only agent with any significant activity against colorectal cancer, is now the base for newer combination regimens that are improving survival in this disease. When irinotecan and oxaliplatin were proven to be active in colorectal cancer, the pursuit of combination regimens began. Targeted agents such as bevacizumab also show activity and improve the outcome of 5-FU-based regimens. The history and development of 5-FU-based treatment regimens that include the newer drugs irinotecan, oxaliplatin, and bevacizumab are discussed in light of the impact these advances have made in the treatment of colorectal cancer