A Study of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

Conditions
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Melanoma, Solid Tumor, Non Small Cell Lung Cancer, Pancreatic Cancer, Ovarian Cancer, Papillary Thyroid Cancer, Colorectal Adenocarcinoma

Intervention / Treatment
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* Drug: CM-24 and Nivolumab - Dose Escalation
* Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
* Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion
* Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
* Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 C, 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A- Dose escalation of CM24 in combination with nivolumab<br> | Drug: CM-24 and Nivolumab - Dose Escalation<br>* Dose escalation of CM24 with nivolumab in adult patients with selected recurrent or metastatic solid tumors<br>|
| Experimental: Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine<br> | Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion<br>* Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer<br>|
| Experimental: Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV<br> | Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion<br>* Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer<br>|
| Experimental: Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine<br> | Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion<br>* Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer<br>|
| Experimental: Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV<br> | Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion<br>* Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer<br>|
| Active Comparator: Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine<br> | Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion<br>* Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer<br>|
| Active Comparator: Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV<br> | Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion<br>* Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Incidence of treatment emergent adverse events | Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors | Up to 24 months | 
| Part C: Safety and tolerability | Incidence of treatment emergent adverse events with CM-24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV in adults with advanced metastatic pancreatic cancer | Up to 24 months | 
| Part D: Overall survival | This is an exploratory randomized sub-study with the objective of estimating the efficacy of CM24 and nivolumab with chemotherapy (Nal-IRI/5-FU/LV or gemcitabine/ nab-paclitaxel) and chemotherapy only (Nal- IRI/5-FU/LV or gemcitabine/nab-paclitaxel) as measured by overall survival. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration [Cmax] | Maximum serum concentration [Cmax] of CM24 | Up to 24 months | 
| Time of maximum concentration [Tmax] | Time of maximum concentration [Tmax] of CM24 | Up to 24 months | 
| Area under the serum concentration curve [AUC] | Area under the serum concentration curve [AUC] of CM24 | Up to 24 months | 
| Half life | Half life of CM24 | Up to 24 months | 
| Drug clearance | Drug clearance of CM24 | Up to 24 months | 
| Volume of distribution | Volume of distribution of CM24 | Up to 24 months | 
| Serum ADA parameters | Serum ADA parameters of CM24 as measured by percentage of patients who are positive for the presence of anti-drug antibodies | Up to 24 months | 
| Objective Response Rate when CM24 is used in combination with nivolumab |  | Up to 24 months | 
| Disease Control Rate when CM24 is used in combination with nivolumab |  | Up to 24 months | 
| Median Duration of Response when CM24 is used in combination with nivolumab |  | Up to 24 months | 
| Median Time to Response when CM24 is used in combination with nivolumab |  | Up to 24 months | 
| Progression Free Survival when CM24 is used in combination with nivolumab |  | Up to 48 months | 
| Overall Survival when CM24 is used in combination with nivolumab |  | Up to 48 months | 
| Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the maximum plasma concentration [Cmax] |  | Up to 24 months | 
| Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the average area under the concentration curve [AUC] |  | Up to 24 months | 
| Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the median area under the concentration curve [AUC] |  | Up to 24 months | 
| Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the maximum plasma concentration [Cmax] |  | Up to 24 months | 
| Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the average area under the concentration curve [AUC] |  | Up to 24 months | 
| Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the median area under the concentration curve [AUC] |  | Up to 24 months | 
| Disease Control Rate when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV |  | Up to 24 months | 
| Duration of Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV |  | Up to 24 months | 
| Time to Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV |  | Up to 24 months | 
| Progression Free Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV |  | Up to 48 months | 
| Overall Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV |  | Up to 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CM24, nivolumab, Opdivo, nab-paclitaxel, Abraxane