A Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors
Considering participating in a START clinical trial?
Study Summary
To evaluate CM-24 in combination with nivolumab in patients with non-small cell lung cancer (NSCLC)
To assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CM24 in combination with nivolumab in adults with advanced solid tumors
To evaluate the safety and tolerability of CM-24 in combination with nivoluma
CEACAM1 measurements in serum, biopsy specimens and TILs as well as tumor and TILs PDL1 levels will be evaluated as potential biomarkers.
Blockade of CEACAM1 by CM24 in combination with nivolumab or nivolumab and nab-paclitaxel, may provide patients with refractory malignancies with an important treatment option.
Safety was assessed according to CTCAE v5 and preliminary anti-tumor activity was assessed by the investigators according to RECISTv1.1 using CT/MRI.
This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A) and advanced metastatic pancreatic cancer (Parts C & D) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV will be administered subsequent to CM24 and nivolumab. CM24, nivolumab and gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV are administered intravenously.
To evaluate CM24 combined with the PD-1 immune checkpoint inhibitor nivolumab and standard of care (SoC) chemotherapy vs. SoC chemotherapy in second line PDAC patients.
To present the interim efficacy and safety data in patients (pts) with advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) who progressed after 1st line therapy, treated with CM24, nivolumab (nivo) and chemotherapy vs. chemotherapy (CH).
To evaluate CM24 in combination with PD-1 inhibitor nivolumab plus standard of care (SoC) chemotherapy in second line pancreatic ductal adenocarcinoma (PDAC) patients compared to SoC chemotherapy alone.
To present the final data and significant efficacy in a biomarker-enriched subgroup.
Serum CEACAM1 and myeloperoxidase (MPO; a NET marker) levels were evaluated by ELISA. Biomarkers were analyzed post-hoc and HRs for various thresholds were correlated with survival outcomes to select the greatest range providing a statistical benefit.
- Part A: Previously treated subjects with recurrent and/or metastatic NSCLC, pancreatic cancer, ovarian cancer, papillary thyroid cancer, colorectal adenocarcinoma and melanoma with documented progression/intolerance following at least one previous therapy (and not more than 2 previous regimens); Part C: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded; subjects with a maximum of 1 prior treatment regimen for metastatic disease excluding: nab-paclitaxel containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #1); fluoropyrimidine or irinotecan containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #2).
- Part D: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded.
- Parts C, D: Subjects who have progressed on or after standard of care chemotherapy with a maximum of 1 prior treatment regimen for advanced metastatic disease:
- Subjects enrolled in arm with gemcitabine/nab-paclitaxel combination should have received a fluoropyrimidine and/or irinotecan containing regimen in the first line of treatment; Prior gemcitabine containing regimen may be allowed only if completed at least 6 months prior to study enrollment.
- Arm #2: Subjects enrolled in arm with Nal-IRI/5FU/LV combination should have received a gemcitabine and/or nab-paclitaxel containing regimen in the first line of treatment; Prior irinotecan and/or fluoropyrimidine containing regimens may be allowed only if completed at least 6 months prior to study enrollment.
- Part A: Availability of an archival tumor sample prior to first treatment. Parts C, D: Fresh tumor biopsy must be obtained within 3 months prior to enrollment and after the last systemic treatment was completed.
- Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy;
- ECOG performance status score of 0 or 1;
- Adequate safety lab results;
- Stable brain metastases;
- WCBP (Women of Childbearing Potential) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test, WCBP must agree to abstain from sex or use an adequate method of contraception, males must abstain from sex with WCBP or use an adequate method of contraception.
- Part A: Received more than two prior systemic regimens for the metastatic disease Parts C and D: Received more than 1 prior systemic regimens for the advanced metastatic disease
- Part A: History of weight loss >10% over the 2 months prior to Screening;
- Unresolved AEs > Grade 1 from prior anticancer therapy.
- Concurrent malignancy requiring treatment;
- Active, untreated central nervous system (CNS) metastases;
- Subjects previously treated with an anti PD-1/PD-L1 targeting agent with history immune mediated toxicity;
- Severely immunocompromised;
- History of allergy or hypersensitivity to any of the study treatment components;
- Major surgery within 4 weeks of study administration;
- Received a live / attenuated vaccine within 30 days of first treatment
- Clinically relevant serious co-morbid medical conditions including, but not limited to:
- Active infection;
- Recent (within six months of Screening) cardiac disease, myocardial infarction, or severe or unstable angina;
- History of serious arrhythmia;
- Chronic obstructive or chronic restrictive pulmonary disease, pulmonary hypertension history of or active interstitial lung disease or pneumonitis;
- Prior organ allograft;
- Subjects with active, known or suspected autoimmune disease;
- History of active or latent tuberculosis infection;
- Positive test for HIV, HBV, or HCV;
- Radiation within two weeks prior to the first study treatment;
- Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
- Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment;
- Pregnant or lactating women
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.